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免疫细胞表面抗原分子CD家族对照表(CD1CD247)
ExalphaBIOLOGicalsproducesandsellsproductsforLifeScienceResearch,includingmonoclonalandpolyclonalantibodies,foruseinimmunohistochemistry,westernblot,ELISAandFlowCytometry.Weofferover800productsand,throughcollaborationswithotherscientistsaswellasourownin-houseR&Dprograms,ExalphacontinuestobringleADIngedgeproductstomarket.OurfamilyofCDantibodiescombinesqualityandperformancewithreasonablepricestomakeourCDantibodiesthebestvalueinthemarkettoday.OurfamilyofProliferationproductsoffereasyall-in-onekitsorstandaloneantibodiestoquantitateproliferatingcells.Takealookatourwebsiteorcallusforadditionalinformation.Note:noinformationisavailableonCDw145,CD181,CD182,CD185-194,CD196-199,CD211,CD214-216,CD218-220,CD237 CD:clusterdesignationofmonoclonalantibodies(clustersofdifferentiation)Designatedatthe1stto7thWorkshopsonInternationalHumanLeukocyteDifferentiationAntigensThelastconferencewasin2000.Thenextconferenceisin2004.HLDAWorkshopsaretheprimarymechanismtocharacterizeleukocytesurfaceantigenicmoleculesandepies;erythroidantigensarenowincludedFor1stto6thworkshops,antibodiesweresubmittedtotheorganizinglaboratory,codedandsenttoparticipatinglaboratoriesfortestingagainstvariouscelltypes.Forthe7thworkshop,aCDdesignationcouldbeestablishedforamoleculeifitsgenehasbeenclonedandatleastonespecificmonoclonalantibodyhadbeenstudiedintheWorkshopInterpretationshouldbebasedoncellulardistributionofstaining,proportionofpositivelystainedcells,stainingintensityandcutofflevels. Familyofnon-polymorphicMHCclassI-likeglycoproteinsAlsomemberofimmunoglobulinsuperfamilyOnchromosome1q22-23(notMHClinked)Has5differentsubsets,allnoncovalentlyassociatedwith12kdbeta2microglobulinFunction:restrictTcellresponsestocertainantigens;maymediatethymicTcelldevelopmentPositivestaining(normal):corticalthymocytes(70%),activatedTcells,Langerhanscells,interdigitatingdendriticcellsPositivestaining(disease):preTALLwithcorticalthymocytephenotype;LangerhanscellhistiocytosisNegativestaining:matureperipheralTcells Positivestaining(normal):Dendriticcellsindermis/epidermisofbenigninflammatoryskindisordersPositivestaining(disease):Langerhanscellhistiocytosis(fairlyspecific),myeloidleukemias,someBcellmalignancies;dendriticcellsinmostperipheralcutaneousTcelllymphomas,AJCP2001;116:72Negativestaining:normalBcells,mostcutaneousperipheralBcelllymphomas(?reflectsreplacementofreactivepatterncontainingdendriticcellswithaneoplasticpatternofBcells)Microimages:LangerhanscellhistiocytosisMicroimages(AJSPsubscribers):pulmonaryLangerhanscellhistiocytosisMicroimages(HumPathsubscribers):LangerhanscellhistiocytosisReferences:AJSP2001;25:630 Positivestaining(disease):myeloidleukemiasandsomeBcellmalignanciesNegativestaining:normalBcells Positivestaining(normal):subsetofnormalperipheralBcellsPositivestaining(disease):myeloidleukemiasandsomeBcellmalignanciesNegativestaining:normalBcells AkaErosettereceptor,LFA-2(leukocytefunctionantigen)Function:bindsCD58/LFA-3onantigen-presentingcells,andinducescostimulatorysignalsinTcellsAlsoregulatesTandNK-mediatedcytolysis,inhibitsapoptosisofactivatedperipheralTcells,mediatesTcellcytokineproduction,regulatesTcellanergyPositivestaining(normal):thymocytes(95%),matureperipheralTcells(almostall),NKcells(80-90%),thymicBcells(50%)Microimages:extranodalNK/Tcelllymphoma,nasaltype AkaOKT3Function:complex(5chains)ofintegralmembraneglycoproteinsassembledasacomplex;haslongcylasmictailwithantigenrecognitionactivationmotif;complexisthendownregulatedAlsosuBDividedintodelta,epsilon,gammasubtypesCylasmicexpressionatearlyTcelldifferentiation,thenmembranousexpressionMostspecificTcellantibodyPositivestaining(normal):thymocytes,peripheralTcells,NKcells;alsoPurkinjecellsofcerebellumPositivestaining(disease):80%ofTcelllymphomasNegativestaining:gammadeltaTcellreceptors,mostBcelllymphomasMicroimages:CD3epsilon-testicularNK/Tcelllymphoma(figure3D)Microimages(AJSPsubscribers):achalasia,post-transplantlymphoproliferativediseaseinliverReferences:AJSP2001;25:1413 AkaOKT4,Thelper/inducerOnchromosome#12pNonpolymorphousglycoproteinsbelongingtoimmunoglobulinsuperfamilyServesasHIVreceptoronTcells(asdochemokinereceptorsCCR5andCXCR4),macrophages,brainCD4+TcellsarekilledbyHIVCoreceptorinMHCclassII-restrictedantigeninducedTcellactivationBindstononpolymorphicregionofclassImolecules;mayincreaseAvidityofcell-cellinteractionsPositivestaining(normal):thymocytes(80-90%),matureTcells(65%,ThelperandCD4/CD8+thymocytes),macrophages,Langerhanscells,dendriticcells,granulocytesPositivestaining(disease):pityriasislichenoidesMicroimages:acutedemyelinatingdisease,extranodalNK/Tcelllymphoma,nasaltype BelongstoancientscavengerreceptorfamilyIsphysicallyandfunctionallycoupledwithTcellreceptor-zeta-CD3signaltransducercomplexCD5+Bcellsproduce“generalistantibodies”-polyreactivelowaffinity"natural"antibodiestoexogenousantigens(tetanustoxoid,lipopolysaccharide)aswellasautoreactiveantibodies(ssDNA,thyroglobulin,insulin)Note:sharksonlyhavepolyreactiveIgMNote:monoreactiveIgGisproducedby<0.1%ofcirculatingBcells,frompositiveselectionandsomaticpointmutationFirstlineofdefenseagainstantigens;havealowactivationthreshold;aretheonlylineofdefenseforthosewhocannotproducespecificantibodyProduceantibodiesusinggermline(nonmutated)configurationofgenesegments,usuallyIgMProductionelevatedinrheumatoidarthritis(27-52%ofcirculatingBcellsvs.20%normal)CD5mayserveasadualreceptor,givingeitherstimulatoryorinhibitorysignalsdependingbothonthecelltypeandthedevelopmentstage Positivestaining(normal):Bcellsofmantlezoneofspleenandlymphnodes;Bcellsinperitonealandpleuralcavities;almostallTcells; Infetus,mostBcellsinspleenandcordbloodareCD5positive Positivestaining(disease):BcellCLL/SLL,mantlecelllymphoma,mostTmalignancies,thymiccarcinomas(70%) Negativestaining:spindlecellthymomas,MALTlymphoma,follicularlymphomaMicroimages:extranodalNK/Tcelllymphoma,nasaltype,mantlecelllymphoma(figure3D) AdhesionmoleculemediatingthebindingofdevelopingthymocyteswiththymicepithelialcellsMaybeinvolvedinautoimmunityandgraftvs.hostdisease(GVHD)AntibodiestoCD6areusedtodepleteTcellsfrombonemarrowtransplantstopreventGVHDPositivestaining(normal):lowlevelsonimmaturethymocytes,highlevelsonmaturethymocytes MembraneglycoproteinandFcreceptorforIgMHomologoustoTCRgamma,IgkappaMembraneexpressionearlyduringTontogeny,beforeTCRrearrangement,persistsuntilterminalstagesofTcelldevelopmentLowerexpressioninmemoryTcellsvs.naiveTcells Negativeexpression:BcellALL,Sezarysyndrome,adultTcellleukemia/lymphomaMicroimages:extranodalNK/Tcelllymphoma,nasaltype AkaOKT8,Tcellsuppressor/cytotoxiccellsOnchromosome#2MHCclassIrestrictedreceptor;bindstononpolymorphicregionofclassImolecules;mayincreaseavidityofcell-cellinteractionsAssociatedwithlymphoepithelioma-likecarcinomaoflung(AJSP2002;26:715) Positivestaining(normal):Tcells(25-35%ofmatureperipheralTcells,mostcytotoxicTcells,CD4/CD8+thymocytes);NKcells(30%-whicharealsoCD3negative);corticalthymocytes(70-80%),epidermotrophiclymphocytesinmycosisfungoides(AJSP2002;26:450) Microimages:lymphoepithelioma-likecarcinomaofcervix-figure3,acutedemyelinatingdisease Microimages(ModPathsubscribers):nodalcytotoxicTcelllymphoma Reference:ModPath2002;15:1131 MaymediateplateletactivationandaggregationAntibodiesareusedtopurgebonemarrowpriortoperipheralstemcellbonemarrowtransplantViralco-receptorPositivestaining(normal):preBcells,Bcellsubset,Tcells,macrophages,platelets,eosinophils,basophils,megakaryocytes,endothelialcells,brain,peripheralnerve,vascularsmoothmuscle,cardiacmuscle,epithelia AkaCommonAcuteLymphoblasticLeukemiaAntigen(CALLA),neutralendopeptidase24.11,neprilysin,enkephalinaseCellmembranemetallopeptidase,characteristicMarkeroffollicularcentercellsandfollicularlymphoma,butalsowidelydistributedinnormaltissueandneoplasms;alsolocalizedtobrushborderinsmallbowelmucosaInactivatesbioactivepeptidesUses:Acutelymphoblasticleukemia:oneoffirstmarkerstoidentifyleukemiccellsinchildren(henceitsname)Breast:markerofmyoepithelialcells,ModPath2002;15:397Burkittlymphoma:confirmdiagnosisColoniccarcinogenesis:increaseinstromalcellsfrommildtoseveredysplasiatoinvasivecarcinoma,HumPath2002;33:806-811Endometriosis:helpfulinidentifyingareasofendometriosisifsparseglandulartissueFollicularlymphoma:toconfirmdiagnosisHepatocellularcarcinomavs.nonhepatocellularcarcinomas:68%sensitiveand>95%specificwithcanalicularpattern,AJSP2001;25:1297,AJSP2002;26:978,althoughanotherstudyrecommendsHepatocyte,MOC31,andpCEAbutnotCD10,ModPath2002;15:1279Microvillousinclusiondisease:strongCD10+cylasmicstainingvs.linearbrushborderstaininginnormals,AJSP2002;26:902Positivestaining(normal):adrenalcortex,pre-Bcells,brain,choroidplexus,corticalthymocytes,endometrialstroma,follicularcentercells,granulocytes,kidneymicrovilli,liver,lymphohemaoieticprecursors,maleGUepithelium,mesonephricremnants,myoepithelialcells(breast),neutrophils,ovary,placenta(cytotrophoblast,intermediatetrophoblast,syncytiotrophoblast),smallintestine(linearbrushborderstaining)Positivestaining(disease):adenomyosisofendometrium,preBALL(75%),CMLinblastcrisis(90%),coloniccarcinoma,dermatofibroma,dermatofibrosarcoma,endometrialadenocarcinoma(maybepresentindesmoplasticstroma),endometrialstromaltumors,follicularcentercelllymphomas,gastriccarcinoma,glioma,hepatocellularcarcinoma(canalicularpatternsimilartopolyclonalCEA),malignantmixedmulleriantumors,mediastinalgermcelltumors,melanomas,mesonephrictumors,microvillousinclusiondisease(strongcylasmicstaining),mullerianadenosarcoma,pancreaticadenocarcinoma,pancreaticsolid-pseudopapillarytumor,placentalsitetrophoblastictumor,primarymediastinalBcelllymphomas(some),prostatecarcinoma,renalcellcarcinoma,renalcellsarcoma,rhabdomyosarcomaandothersarcomas,schwannoma,tumorofwolffianoriginofbroadligamentandovary,urothelialcarcinoma,uterinecarcinoma,uterinecellularleiomyomas(50%),uterineleiomyosarcomasandotheruterinesarcomasNegativestaining:myeloidanderythroidprecursors,otherfemalegenitaltracttumors(includingclearcellcarcinomas)Microimages:follicularcentercells(figure1),intranodalheteroicmammaryducts(figure1C),Microimages(AJSPsubscribers):endometrialstromaltumor#1(negative),#2,hepatocellularcarcinoma#1,#2,mesonephriccarcinomaofuterus,mesonephricderivativesinmen,microvillousinclusiondisease#1,#2(controls),vulvar,vaginalandcervicallesions,uterusandtrophoblast,fallopiantubeandovaryMicroimages(HumPathsubscribers):canalicularpatterninhepatocellularcarcinoma(figureC),gastriccarcinomaatapicalborder(figureB),colonicadenoma,coloniccarcinoma#1,#2Microimages(ModPathsubscribers):canalicularpatterninhepatocellularcarcinoma(figureB),malignantmixedmulleriantumor#1,#2,#3,breastmyoepithelium,breastadenosis,breastDCIS,invasiveductalcarcinomaofbreast,diffuselargeBcelllymphoma,adenomyosisReferences:AJSP2002;26:978,AJSP2001;25:1540,AJSP2002;26:902,AJSP2003;27:178,ModPath2002;15:1279,ModPath2002;15:923,ModPath2002;15:397,ModPath2002;15:413,ModPath2002;16:22 CD11a,bandcallhavesamebetachain(CD18)Membersofintegrinreceptorfamily;heterodimersofnoncovalentlyassociatedalphaandbetasubunits AkaalphaL;LFA-1(incomplexwithCD18)AnalphaintegrinchainthatbindstoCD18andmediatesleukocyteadhesionandlymphocyterecirculationthroughlymphnodesWithCD18,bindstoICAM-1(CD54,leukocyteadhesionmolecule)andICAM-2(CD102)Facilitateslymphocyteblastogenesis,cellularcytotoxicity,lymphocyte-endothelialcelladhesion,andbindingtounopsonizedbacteria(E.coli)andfungi(Hislasmacapsulatum)Note:patientswithleukocyteadhesiondeficiency(mutationsinCD18)haveoftenfatalimmunodeficiencyearlyinlifeMarkerofdifferentiationinacutepromyelocyticleukemiaPositivestaining(normal):allleukocytesNegativestaining:platelets AkaCR3,iC3breceptorMediatesphagocytosisofparticlesopsonizedwithiC3bFacilitatesneutrophilaggregation,adhesiontosubstratesbyopsonization,chemotaxisLigandsincludefibrinogen,FactorX,ICAM-1,Saccharomycescerevisiae,Staphylococcusepidermidis,Hislasmacapsulatum,Note:C3iscommontoclassicalandalternatecomplementpathway,andservesasanamplificationstepC3b(activatedC3)canamplifybycleavingmoreC3viathealternatecomplementpathwayPositivestaining(normal):folliculardendriticcells,granulocytes,macrophages,myeloidcellsbeginningwithpromyelocytes,NKcells,someB/TcellsPositivestaining(disease):AML-M1-M3(35-70%),M4-M5(80-90%);hairycellleukemia(virtuallyall) AkaCR4,iC3breceptorClearsopsonizedparticlesandimmunecomplexes;alsobindstofibrinogenandisinvolvedinadhesionofmonocytesandneutrophilstoendotheliumMemberofbeta2familyofintegrinreceptorsPrognosticvalue:associatedwithgoodprognosisinB-CLLPositivestaining(normal):50%ofactivatedCD4/CD8+Tcells;granulocytes,lymphocytes,macrophages,NKcellsPositivestaining(disease):AML-M4-M5(50%);hairycellleukemia(virtuallyall),B-CLL Positivestaining(normal):granulocytes,monocytes,NKcells,plateletsNegativestaining:basophils,bonemarrowprecursors,AML AkaAminoPeptidaseN,APNMyeloidantigen,althoughCD33ismorespecificPeptidecleavingenzymeofbrushbordermembranesofsmallintestine,renalproximaltubulesandplacentaAlsopresentonCNSsynapticmembranesReceptorforonestrainofhumancoronavirusthatcausesmanyupperrespiratorytractinfectionsDefectsappeartocausevariousleukemias/lymphomasServesanimportantfunctionforearlyCMVinfectionCD13autoantibodiesarestronglyassociatedwithchronicgraftversushostdiseaseafterbonemarrowtransplantationPositivestaining(normal):bileductcanaliculi,centralnervoussystemsynapses,endothelialcells,fibroblasts,granulocytes(most),largegranularlymphocytes(some),macrophages,osteoclasts,perineuriumofperipheralnerves,placenta,renalproximaltubules,smallintestinePositivestaining(disease):AMLM1-M5(75-95%),M6(usually),CML(90%);preBALL(7-10%),preTALL(rare) Akalipopolysaccharide(LPS)receptor,endotoxinreceptorBindingofLPStoCD14onmacrophagescausestheiractivationandreleaseofcytokinesInvolvedintheclearanceofapoptoticcellsAlsoregulatesIgElevelsPositivestaining(normal):macrophages/monocytes(90%),granulocytes-weak(30%),Langerhanscells;dendriticcells,BcellsPositivestaining(disease):B-CLL(90%),follicularcentercelllymphoma(80%),diffuselargeBcelllymphoma(40%);AML-M4/M5(50-90%)Negativestaining:myeloidProgenitors,AMLM3,M6,M7,M0-M2(usually) AkaLeuM1,Lacto-N-FucopentoseIIIceramideRecognizesHaptenX,acarbohydratelinkedtocellmembraneproteinsofmyelomonocyticcellsPositivestaining(normal):myeloidcells(90%);activatedBandTcells(includinginfectiousmononucleosis);eosinophilsstainintenselyPositivestaining(disease):Reed-Sternbergcells,20%ofTcelllymphomas,5%ofBcelllymphomas,50%ofcarcinomasNegativestaining:erythroidcells,platelets;ALLMicroimages:Reed-Sternbergcells-figure3A,primarypulmonaryHodgkin’slymphoma-figure3A AkaSialylLewisX;ligandforCD62PandCD62EPositivestaining(normal):granulocytes,macrophages AkasulfatedCD15 AkaFcreceptorIIIAImportantforAbdependentcytotoxicityofforeigncellsIftargetcellhasclassIMHC,thenNKcell"skillercellinhibitoryreceptor(KIR)inhibitscytolysis Positivestaining(normal):NKcells(10-20%),granulocytes,monocytes(rare),alveolarmacrophages(common),Tcells(some)Negativestaining:Myelodysplasticsyndrome AkaFcreceptorIIIBPositivestaining:neutrophils AkaLactosylceramideBindstobacteriaandmayfunctioninphagocytosisPositivestaining(normal):granulocytes,macrophages/monocytes,platelets,basophils,CD19+Bcells,tonsillardendriticcells Formsthebeta2chainofCD11a,b,c(leukocyteadhesionmolecule)Importantforadhesionandsignalinginthehemaoieticsystem(seeCD11a-cabove)LeukocyteAdhesionDeficiency(LAD-1)causedbyCD18defectcodingforcommonb2subunit;patientssufferfromrecurrentinfectionsPositivestaining:leukocytes ResponseregulatorthatplaysadominantroleinestablishingsignalingthresholdsforantigenreceptorsandothersurfacereceptorsonBcells;alsoregulatesBcelldevelopment,activationanddifferentiationCD19antibodyinhibitsBcellactivationfromanti-immunoglobulinCoreceptorwithCD21EarliestBcellantigeninfetaltissue Positivestaining(normal):PreB,Bcells;firstBcellantigenafterHLA-DR,folliculardendriticcells Negativestaining:plasmacells AkaL2633kdphosphoproteinwith3hydrophobicregionsthattraversethecellmembrane,creatingastructuresimilartoanionchannelDeliversearlysignalinBcellactivation,allowingrestingBcellstorespondtolaterantigensRituximabisachimericmurine-humananti-CD20antibodyusedfortreatmentofBcelllymphomasUses:commonlyusedmarkerforBcells Positivestaining(normal):MostBcells(afterCD19andCD10expression,beforeCD21/22expressionandsurfaceimmunoglobulinexpression),retainedonmatureBcellsuntilplasmacelldevelopment;alsofolliculardendriticcells Positivestaining(disease):90%ofBcelllymphomas,40%ofpreBALL/LBL;80%oflymphocytepredominantHodgkin’slymphoma,dimlyexpressedinTcells(benignandneoplastic),spindlecellthymomasNegativestaining:non-hemaoieticcells,mostTcells,plasmacellsMicroimages:largeBcelllymphoma,CNSdiffuselargeBcelllymphoma(figureA),lymphoplasmacyticlymphoma/Waldenströmmacroglobulinemiainbrain-figureDMicroimages(ModPathsubscribers):post-transplantlymphoproliferativedisorderReferences:ModPath2002;15:647 AkaCR2,C3dreceptor,EBVreceptor BindstoEpsteinBarrvirusandbreakdownproductsofcomplementcomponentC3 FormsasignalingcomplexwithCD19,CD81andCD225 BothCD21andCD23aredendriticcellmarkers Hodgkin’slymphomademonstratesdisruptionoffolliculardendriticcell-germinalcellclusters(evaluatedbyCD21andCD23) Microimages(AJSPsubscribers):inflammatorypseudotumor-likefolliculardendriticcelltumorA,B,Hodgkin’slymphomaA,BMicroimages(ModPathsubscribers):extranodalfolliculardendriticcellsarcomaReferences:AJSP2001;25:721,AJSP2001;25:388,ModPath2002;15:50 Negativestaining:plasmacells AkalowaffinityIgEreceptorRegulatesIgEsynthesisbynegativefeedbackTriggersmonokinerelease(TNF,IL-1,IL-6,GM-CSF)bymonocytesAfterphysiologicgerminalcelldevelopment,thefolliculardendriticcellmeshworkexpandsandfolliculardendriticcellsinthelightzoneofthegerminalcenterbecomeCD23positiveCD23alsoactsasBcellgrowthfactor,promotingdifferentiationintoplasmacells BothCD21andCD23aredendriticcellmarkers Positivestaining(normal):ActivatedmatureBcellsexpressingIgMorIgD,monocytes/macrophages,Tcellsubsets,platelets,eosinophils,Langerhanscells,folliculardendriticcells Positivestaining(disease):B-cellCLL/SLLNegativestaining:otherBcells;mantlecelllymphoma ExpressedathighlevelsinsmallcelllungcarcinomaPositivestaining(normal):allBcells,granulocytes,kidneycells,epithelialcellsPositivestaining(disease):carcinomas,mostpre-BALL/LBL,virtuallyallBcelllymphomasNegativestaining:plasmacells,multiplemyeloma,Tcells,monocytes,redbloodcells,platelets AkaIL-2receptoralphachain,existsinatleast3formsLimitedexpressionmaysafeguardagainstcatastrophicT-cellproliferationbyimmunogenicstimulus.Positivestaining:ActivatedB,T,macrophagesPositivestaining(disease):hairycellleukemia AkadipeptidylpeptidaseIV,adenosinedeaminasecomplexingprotein2CostimulatorymoleculeinTcellactivationCofactorwithCD4forHIVentryintocellsPositivestaining(normal):ActivatedT,Bcells,NKcells,macrophages,renalproximaltubularepithelialcells,smallintestinalepithelium,biliarycanaliculae,splenicsinusliningcellsNegative/dimstaining:Tcellsinperipheralbloodofmycosisfungoidespatients,AJCP2001;115:885 MarkerofTcellactivationCD27/CD70interactionsalsoregulateBcellproliferationandTcelldifferentiationPositivestaining:Tcells,memoryBcells Celladhesionmolecule;co-receptorforBcell-TcellcooperationPromotesTcellactivationReceptorforCD80(B7)&CD86(BB1),foundonactivatedBcellsConstitutive,highabundance,lowaffinityreceptor;oppositesignalsaremediatedbyCTLA4(CD152)ResultofTcellantigenstimulationdependsonsumofeffectsofTcellreceptor,CD28anditsligand,CTLA4anditsligandCD8+,CD28+TcellsmediateantigenspecificcytotoxicTcells(classIrestricted)(90%ofCD8+Tcells)CD8+,CD28-TcellsmediatesuppressorTcells(10%ofCD8+Tcells)Positivestaining(normal):CD4+Tcells(95%),CD8+Tcells(50%);activatedBcells,plasmacellsReference:186760 AkaplateletGPIIa,beta-1integrin,fibronectinreceptorPositivestaining(normal):fibroblasts,platelets,Tcells AkaKi-1,Ber-H2Lymphocyteactivationantigen,relatedtotumornecrosisfactorDoesn’tworkwellwithB5fixedtissueMaybeinvolvedinnegativeTcellselectioninthymusInterpretation:membranousstainingPositivestaining(normal):granulocytes,plasmacells,activatedB,TandNKcellsPositivestaining(disease):infectiousmononucleosis,lymphocytesinfectedwithHIV,HTLV-1,EBV,HHV8orhepatitisB;Reed-Sternbergcells,90%ofanaplasticlargecelllymphomas,lymphomatoidpapulosis,peripheralT-celllymphomas,embryonalcarcinomaoftestis,primaryeffusionlymphomaMicroimages:Hodgkin’slymphoma#1,#2,#3-figure3B(primarypulmonary),#4-figure3B,anaplasticlymphoma,embryonalcarcinoma-figure6,intratubularembryonalcarcinoma-figure4Microimages(HumPathsubscribers):anaplasticlargecelllymphoma(figureE),AIDSrelatedprimaryeffusionlymphoma(figureD) Akaplateletendothelialcelladhesionmolecule,PECAM-1Encodedon#17MostsensitiveandspecificendothelialmarkerinparaffinsectionsImportantroleindiapedesisstepofleukocyteemigrationininflammation;alsoangiogenesisNote:don’tconfuseCD31+macrophages(granular,membranousexpression)withavasculartumor,AJSP2001;25:1167Sensitiveformalignantvasculartumors;maybelesssensitiveforbenignlesionsInterpretation:membranousstain(notcylasmic);endotheliumisapositiveinternalcontrolPositivestaining(normal):endothelium,platelets,macrophagesandKupffercells,granulocytes,T/NKcells,lymphocytes,megakaryocytes,fibroblasts,osteoclasts,neutrophilsPositivestaining(tumors):epithelioidhemangioendothelioma;epithelioidsarcoma-likehemangioendothelioma(AJSP2003;27:48);othervasculartumors,histiocyticmalignancies,plasmacytomas;rarecarcinomasandsarcomasMicroimages:epithelioidangiosarcoma(figure1A)Microimages(AJSPsubscribers):epithelioidsarcoma-likehemangioendothelioma,epithelioidhemangioendothelioma,epithelioidangiosarcoma,CD31+macrophages,malignanthistiocytosisMicroimages(HumPathsubscribers):hepaticcavernoushemangiomas(figure2B)Microimages(ModPathsubscribers):angiosarcoma(figureE)References:AJSP2001;25:684,ModPath2002:15;434 AkaFcgammaRIILowaffinityreceptorthatbindstotheFcregionofIgGimmunecomplexesIfBcellsarestimulatedsothatsurfaceimmunoglobulinreceptorsarecoclusteredwithCD32receptors,BcellsdoNOTproliferativeandmayundergoapoptosisinsteadofproliferationPositivestaining:macrophages,granulocytes,Bcells,eosinophils,basophils,platelets Myeloidcellantigen(alsoCD13);asialoadhesinthatmaymediatecell-to-celladhesion,actsasareceptorthatinhibitstheproliferationofnormalandleukemicmyeloidcellsPositivestaining(normal):Precursormyeloidcells;mostmonocyticcells,epidermalLangerhanscells(variable)Positivestaining(disease):AMLM1-M5(75-85%),M7(variable),CML(90%);blasts(all),someALLNegativestaining:granulocytes,maturebonemarrowcells,non-myeloidcells Cell-celladhesionmoleculeandcellsurfaceglycoproteinMaymediateattachmentofstemcellstobonemarrowextracellularmatrixordirectlytostromalcellsAntibodiesareusedtoquantifyandpurifylymphohemaoieticstemcell/progenitorcellsforresearchandforclinicalbonemarrowtransplantation;however,countingCD34+mononuclearcellsmayoverestimatemyeloidblastsinbonemarrowsmearsduetohematogonesandCD34+megakaryocytes,Archives2002;126:823Interpretation:membranousstain;endotheliumactsasapositiveinternalcontrolUses:possIBLyconfirmchronicintestinalpseudo-obstruction,AJSP2003;27:228Positivestaining(normal):hemaoieticprogenitorcells,vascularendothelialcells(thesecellsareTdT+,HLA-DR+)Positivestaining(disease):alveolarsoftpartsarcoma,preB-ALL(75%),AML(40%),AML-M7(most),chordoidgliomas,dendriticfibromyxolipoma,dermatofibrosarcomaprotuberans,epithelioidsarcomas,gastrointestinalstromaltumors,giantcellfibroblastoma,granulocyticsarcoma,hamartomatoustumorsofchronicdrugresistantepilepsy,hemangiopericytomas(50%),inflammatoryfibrouspolypsofstomach(HumPath2002;33:307),Kaposi’ssarcoma(strong,diffuseinspindlecells),liposarcomas(myxoid,pleomorphic),MFH,malignantperipheralnervesheathtumors,meningealhemangiopericytomas,meningiomas(some),metanephricadenosarcomaofkidney(stromaonly),myelodysplasticsyndrome(myeloidblasts),myofibroblastomaofbreast,neurofibromas,nuchalfibromas(alsoCD99+),papillarythyroidcarcinoma,paratesticularleiomyosarcoma(30%),pleomorphichyalinizingangiectatictumor,pseudoangiomatousstromalhyperplasiaofbreast,schwannomas(usually),sclerosingliposarcoma(spindleandatypicalcells),solitaryfibroustumors,synovialsarcoma(focalin6%ofmonophasictumors),blastsintransientmyeloproliferativedisorderNegativestaining:Ewing’ssarcoma/PNET,myofibrosarcomaofbreast,inflammatorymyofibroblastictumorsofstomachMicroimages:granulocyticsarcoma,malignantsolitaryfibroustumor,GISTandsolitaryfibroustumor,GIST(figureB),CD34+blastsandmegakaryoctyes,cavernoushemangiomaofspermaticcord,solitaryfibroustumoroforbitMicroimages(AJSPsubscribers):hybridDFSP-giantcellfibroblastoma,solitaryfibroustumorofkidney,metanephricadenosarcomaofkidney(stromaonly),rectalGIST(figureB),paratesticularleiomyosarcoma,normalsmallbowel(figure1B),normalcolon(figure1B),chronicintestinalpseudo-obstruction(figure1B),Gardnerassociatedfibromas,microcysticadnexalcarcinomaA,BMicroimages(ModPathsubscribers):GIST(figuresC,D)Reference:Archives2002;126:1189,AJSP2003;27:27,AJSP2002;26:932,AJSP2001;25:1451,AJSP2001;25:1194;AJSP2001;25:645,AJSP2001;25:464,ModPath2002;15:125 AkaCR1,C3bandC4breceptorMediatesadherenceofimmunecomplexescoatedwithC4b/C3bandtheirtransporttothefixedphagocytesystemsofthespleenandliverCofactorforspecificproteolyticcleavageofC3bandC4bbyplasmaserineproteasefactorI,whichlimitscomplementactivationandproducesligandsforothercomplementreceptorsTheKnops,McCoy,Swain-Langley,andYorkbloodgroupantigensarelocatedonCD35Positivestaining:granulocytes,macrophages,Bcells,Tcells(10%),NKcellsubset,erythrocytes,folliculardendriticcells,eosinophils,glomerularpodocytes,someastrocytesMicroimages(AJSPsubscribers):inflammatorypseudotumor-likefolliculardendriticcelltumorA,BMicroimages(ModPathsubscribers):extranodalfolliculardendriticcellsarcoma(figure7B)Reference:AJSP2001;25:721,ModPath2002;15:50 AkaplateletGPIVorGPIIIb;thrombospondinreceptorScavengerreceptorfor50%ofoxidizedLDLandshedphotoreceptoroutersegmentsCelladhesionmoleculeinplateletadhesionandaggregation,platelet-monocyteandplatelet-tumorcellinteractionSiteofcytoadherenceofPlasmodiumfalciparuminfectederythrocytestomicrovascularendothelialcellsCD36deficiencyfrequentinsub-SaharanAfrica,Asia;associatedsurprisinglywithsusceptibilitytoseverecerebralmalariaDevelopmentofanti-CD36antibodiescancauseseriouscomplicationsinmultiplytransfusedpatients(sicklecelldisease)Positivestaining(normal):platelets,macrophages,endothelialcells,earlyerythroidcells,megakaryocytesPositivestaining(disease):AMLM4-M7Negativestaining:AMLM0-M2(usually),M3 Positivestaining(normal):Bcells,Bcelllymphomas,lowlevelsonTcells,neutrophils,granulocytes,monocytesPositivestaining(disease):hairycellleukemia Novelenzymecapableofcatalyzingmultiplereactions;twoenzymeproductsarecalciummessengersPositiveandnegativeregulatorofcellactivationandproliferation,dependingonthecellularenvironmentInvolvedinadhesionbetweenhumanlymphocytesandendothelialcellsImportantforleukemiaphenotypingandclassification,targetingofimmunotoxinantibodyinmyelomatreatmentIncreaseswithHIVSEROconversion;coexpressionwithCD8associatedwithprogression(indicatespersistentviralstimulation)Positivestaining(normal):plasmacells(strong),lymphoidprogenitorcells,NKcells,BandTcells,monocytes,erythroidandmyeloidprecursors,thymocytes,blasts,brain,muscle,kidney,liver,ovary,pancreas,placenta,testisPositivestaining(disease):lymphoma,neuroblastoma AkavascularATPdiphosphohydrolasePlasmamembrane-boundenzymethathydrolyzesextracellularATPandADPtoAMPImportantinhibitorofplateletactivationPositivestaining(normal):B,TandNKcells,endothelialcells,placenta Playsacentralroleinregulatingcell-mediatedimmunityandantibodymediatedimmunityMaymediateinflammatorycomponentofatherogenesisPositivestaining(normal):Bcells,macrophages,dendriticcells,endothelialcells,fibroblasts,keratinocytesPositivestaining(disease):carcinomas,mostBcelllymphomas,B-ALL(some)Negativestaining:plasmacells AkaplateletGPIIbReceptorforfibrinogenin,vonWillebrandfactorandfibronectinMutationscausethrombastheniaPositivestaining(normal):platelets,megakaryocytesPositivestaining(disease):AMLM7,blastsintransientmyeloproliferativedisorder AkaplateletGPIXCD42a-dcomplexisreceptorforvonWillebrandfactorandthrombinActualbindingsiteofvWfandthrombinisonCD42bThiscomplexmediatesadhesionofplateletstosubendothelialmatricesexposedupondamagetoendotheliumandamplifiesplateletresponsetothrombinAbsenceofCD42complex(mutationsinCD42a-c)causesBernard-Souliersyndrome(BSS),ableedingdisorderwiththrombocyeniaandgiantplateletsPositivestaining(normal):plateletsandmegakaryocytes AkaplateletGPIbalphaCD42a-dcomplexisreceptorforvonWillebrandfactorandthrombinActualbindingsiteofvWfandthrombinisonCD42bPositivestaining(normal):plateletsandmegakaryocytesPositivestaining(disease):blastsintransientmyeloproliferativedisorder AkaplateletGPIbbetaPositivestaining(normal):plateletsandmegakaryocytes AkaplateletGPVCD42dmousemonoclonalantibodiesareusedtodetectauto-andallo-anti-plateletantibodiesCo-expressionstudiessuggestthatCD42dmaybeessentialtoformthehighaffinitythrombinreceptorPositivestaining(normal):plateletsandmegakaryocytes Akaleukosialin,sialophorinAppearstobeananti-adhesivemoleculemediatingrepulsionbetweenleukocytesandothercells,althoughitmayactasanadhesionmoleculeunderothercircumstancesExpressiondefectiveinWiskott-Aldrichsyndrome,althoughsecondarytoXlinkedgeneticdefect;causesdefectsincytotoxicandhelperTcellfunctionsPositivestaining(normal):MostTcells,activatedBcells,NKcells,granulocytes,monocytes,megakaryocytes,brainPositivestaining(disease):80%ofTcelllymphomas;coexpressedwithCD20inSLLbutnotbenignlesions;granulocyticsarcomas,AML,mostALL"s,plasmacytomas;mastcelldisease(alsopositivefortryptase,CD68,CD117)Microimages:granulocyticsarcoma,mantlecelllymphomaMicroimages(AJSPsubscribers):chronicactivemyocarditis(figureB) FamilyofcellsurfaceglycoproteinswithisoformsgeneratedbyalternatesplicingofmRNAImportantinepithelialcelladhesiontohyaluronateinbasementmembranesandmaintainingpolarorientationofcells;alsobindslaminin,collagenandfibronectinMayhelplymphomasdisseminatebybindingtohighendothelialvenulesInvolvedinleukocyteattachmentandrollingonendothelialcells,homingtoperipherallymphoidorgansandsitesofinflammationandleukocyteaggregationUses:reactiveurotheliumhasdiffusefullthicknessstainingvs.carcinomainsitu,AJSP2001;25:1074Prognosticsignificance:Coloncarcinoma:overexpressionofCD44vpredictsanaggressivecourseEndometrialcarcinoma:lossofCD44relatedtoinvasionLungcarcinoma:lossofCD44relatedtoinvasionLymphomas-diffuselargecellandB-CLL:expressionassociatedwithpoorprognosisNeuroblastoma:lossofCD44relatedtoinvasionProstatecancer:lossassociatedwithpooroutcomeUrothelialneoplasms,papillary:lossofCD44immunoreactivity(restrictedtobasalcelllayerinnormalurothelium)associatedwithincreasingtumorgradeandstageinpTaandpT1patients,ModPath2000;13:1315Positivestaining(normal):whitebloodcells,redbloodcells,breast,colon,stomach,uterus,mosttissue;urothelialbasalcells;reactiveurotheliumhasdiffusefullthicknessstaining(AJSP2001;25:1074)Positivestaining(tumors):80%ofcolorectalcarcinomas;tumorsormucosawithwell-developedsquamousdifferentiationArchives2000;124(2):212Negativestaining:platelets,hepatocytes,cardiacmuscle,kidneytubularepithelium,testis,normalglandulartypeepithelium,welldifferentiatedadenocarcinomas,urothelialcarcinomaMicroimages:CD44sincolonicadenocarcinoma(figureB)Microimages(AJSPsubscribers):normalurothelium(figure1D),reactiveurothelium(figure2D),reactiveurothelium(figure4D) AkaCD44sPrincipalreceptorforhyaluronicacidTheoreticalutilityindifferentiatingmesotheliomasinceitproducesabundanthyaluronicacid,butnotactuallyusefulbecauseCD44Hisreactivein1/3to1/2ofadenocarcinomas,HumPath2002;33:953 Maybeinvolvedinleukocyteattachmentandrollingonendothelialcells,homingtoperipherallymphoidorgansandtositesofinflammationHeterogeneousgroupofCD44variantisoformsexpressedconstitutivelyinepithelialcellsandmonocytelineagecells;upregulatedinactivatedleukocytes Akaleukocytecommonantigen(LCA);atyrosinephosphataseCriticalrequirementforTandBcellantigenreceptor-mediatedactivationTargetofimmunosuppressiveantibodytreatmentMajorcomponentofglycocalyxNegativeinpatientswithseverecombinedimmunodeficiency,characterizedbyadefectinfunctionorBandTcelldevelopment,lymphopenia,anddeficiencyinhumoralandcell-mediatedimmunity.Differentsubsetsofhemaoieticcellsexpressdifferentisoforms,whichcanchangeinresponsetocytokines: CD45RA-naive/restingTcells,medullarythymocytes CD45RO-memory/activatedTcells,corticalthymocytesPositivestaining(normal):allhemaoieticcells,strongerinlymphocytes(10%ofsurfacearea)Negativestaining:redbloodcells,non-hemaoieticcells,lymphoplasmacyticlymphoma,lymphoblasticlymphoma,anaplasticlymphoma,multiplemyeloma,Reed-SternbergcellsMicroimages:Reed-Sternbergcells-CD45negative,figure3C AkaUCHL-1Positivestaining(normal):memoryandactivatedTcells,someBcells,granulocytes(weak),macrophages(weak),corticalthymocytesPositivestaining(disease):75%ofTcellnon-Hodgkin’slymphomas,variableTcellALL/LBL,25%ofAMLNegativestaining:MostBcellnon-Hodgkin’slymphomas,carcinomasMicroimages:nasalNK/Tcelllymphoma(figureC) Akamembranecofactorprotein(MCP)CofactorforFactorIproteolyticcleavageofC3bandC4b;preventsinappropriatecomplementactivation,especiallyviaalternativepathway,bylimitingformationandfunctionofC3convertasesReceptorformeaslesvirusandHHV-6HasmultipleisoformsAcrosomalCD46isexposedonspermheadatcapacitation;mayhelpfusespermatozoaandoocytePositivestaining(normal):allcellsexcepterythrocytes Akaintegrinassociatedprotein(IAP);oneofmanythrombospondinreceptorsSimilartoRh-antigenMayinteractwithintegrinsandmediateintracellularcalciumincreaseduringcelladhesionMayhelpmacrophagesdistinguishselffromforeignsubstancesMayhaveroleingiantcellcreationfrommacrophagefusionPositivestaining(normal):hemaoieticcells,epithelialcells,endothelialcells,fibroblasts,mesenchymalcellsPositivestaining(disease):tumorcelllines AkaRhrelatedantigenSimilartoRh-antigen;mayinteractwithintegrinsPreviouslyCDw149 Mediatesadhesionviaitsreceptor,CD2CD48-positivelymphocytesdecreasedinparoxysmalnocturnalhemoglobinuriaPositivestaining(normal):mostleukocytes,activatedlymphocytesNegativestaining:neutrophils,platelets Akaverylateantigen(VLA)alpha1chain,integrinalpha1chainIntegrinsareintegralcell-surfaceproteinscomposedofanalphachainandabetachain.Agivenchainmaycombinewithmultiplepartnersresultingindifferentintegrins.Verylateactivationproteins(VLA)areafamilyofintegrinsoriginallyidentifiedonactivatedhumanTcells,lateronfibroblasts,platelets,others.Sixforms,VLA1toVLA6,havebeenidentified,eachwithdistinctalphachain(numberedalpha-1toalpha-6)associatedwithacommonbetachain.CD49a-LamininandcollagenreceptorPositivestaining(normal):activatedBandTcells,monocytes Akaverylateantigen(VLA)alpha2chain-onTcellsAkaGPIa/IIawhenexpressedonplateletsReceptorforlaminin,collagen,fibronectin,e-cadherinResponsibleforplateletadhesiontocollagen(bloodclotting),roleinangiogenesisPositivestaining(normal):platelets,activatedB&Tcells Akaverylateantigen(VLA)alpha3chainReceptorforlaminin,collagen,fibronectin,thrombospondinPositivestaining(normal):nonhemaoieticcells Akaverylateantigen(VLA)alpha4chainReceptorforfibronectin,thrombospondin,VCAM-1Roleincell-cellinteractionsandcelladhesiontotheextracellularmatrixPromotes(a)lymphocytemigrationintotissuebystrengtheninglymphocyteadhesiontoendothelialcells,(b)rollingofTcellsinvascularlumenonVCAM-1ofendothelium,(c)homingofTcellsubsetstoPeyer"spatches,(d)differentiationofhemaoieticprecursorcellsbyadhesiontobonemarrowstromalcellsRelevanttotumorprogressionandmetastasisPositivestaining(normal):macrophages,TandBcells,thymocytes,eosinophils,basophils,NKcells,dendriticcells,myeloidcells,erythrocyteprecursorsPositivestaining(disease):melanomacellsNegativestaining:erythrocytes,platelets,neutrophils Akaverylateantigen(VLA)alpha5chain Positivestaining(normal):platelets,monocytes,neutrophils Akaverylateantigen(VLA)alpha6chainLamininreceptorImportantforformationofhemidesmosomesofstratifiedsquamousandtransitionalepitheliaPositivestaining(normal):epithelialcells AkaICAM-3;ligandforLFA-1(CD54)ProvidesadhesionsignalsimportantinB-TcellinteractionsImportantinMHCrestrictedinteractionbetweenTcellsandtargetcellsRegulatesleukocytemorphologyPositivestaining(normal):leukocytes,epidermalLangerhanscells,endothelialcellsNegativestaining:non-hemaoieticcells Akavitronectinreceptor-alphachain;betachainofvitronectinreceptorisCD61Positivestaining(normal):platelets,endothelialcells,megakaryocytes AkaCampath-1CD52antibodiesarelyticfortargetcells,bothwithhumancomplementandviaantibodydependentcellularcytotoxicityCD52antibodiesusedforlong-termdepletionoflymphocytesinvivo,intrialsforCLLandasimmunosuppressant;patientshavehigherriskforopportunitisticinfectionsPositivestaining(normal):thymocytes,lymphocytes,monocytes/macrophages,eosinophils,epithelialcellsliningthemalereproductivetractPositivestaining(disease):mostlymphoidmalignancies(variablelevels),Negativestaining:lymphocytesfrompatientswithPNH,neutrophils(weakerthaneosinophils) Mostspecificandreliablepan-leukocytemarkerMaytransduceCD2-generatedsignalsinTcellsandnaturalkillercellsPositivestaining(normal):leukocytesNegativestaining:platelets,redbloodcells,non-hemaoieticcells AkaICAM-1(intercellularadhesionmolecule1);ligandforLFA-1(CD50)Receptorforrhinovirus,malariainfectederythrocytesInvolvedinadhesionofneutrophilstoendotheliumatsiteofinflammation ReactswithCD11a/CD18orCD11b/CD18resultinginimmunereactionorinflammationPositivestaining(normal):broad,BandTcells,monocytes,endothelialcells,epithelialcells(various)Positivestaining(tumors):keratoacanthoma(moreinfullydevelopedlesionswithinflammatoryinfiltrate),cutaneoussquamouscellcarcinomaMicroimages(ModPathsubscribers):keratoacanthoma,poorlydifferentiatedsquamouscellcarcinomaReference:ModPath2003;16:8 AkadecayacceleratingfactorBindsC3bBb(alternativepathwayconvertase)andC4b2a(classicalpathwayconvertase)toacceleratedecayoftheC3convertases;protectsagainstinappropriatecomplementactivationReceptorforCD97ReceptorforechovirusandCoxsackieBvirusDeficientinredbloodcellsfrompatientswithparoxysmalnocturnalhemoglobinuriaPositivestaining(normal):allhemaoieticcellsandallcelltypesinintimatecontactwithcomplementproteins;alsoepithelialcellsliningextracellularcompartments,bodyfluids,extracellularmatrix AkaN-CAM(neuralcelladhesionmolecule),at#11q23Regulateshomophilic(like-like)interactionsbetweenneuronsandbetweenneuronsandmuscle AlsoassociateswithfibroblastgrowthfactorreceptorandstimulatestyrosinekinaseactivityofreceptortoinduceneuriteoutgrowthWhenneuralcrestcellssmakingN-CAMandN-cadherinandstartdisplayingintegrinreceptors,cellsseparateandmigrateContributestocell-cellorcell-matrixadhesionduringdevelopmentLymphocyteactivatedkillerphenomenonmediatedbyIL-2activatedCD56+,CD3-,NKcellsPrototypicmarkerofNKcells,alsopresentonsubsetofCD4+andCD8+Tcells Negativestaining:PNET/Ewing’ssarcomaMicroimages:testicularNK/Tcelllymphoma(figure3C),extranodalNK/Tcelllymphoma,nasaltype AkaLeu7GlycoproteinwithcelladhesionfunctionsNKcellmarkerandneuroendocrinemarkerSubsetofNKcells(note:NKcellshavenoTCRmembraneexpressionorgenerearrangement)CD16+,CD57-:substantialNKactivityCD16-,CD57-:noNKactivityCD16-,CD57+:weakNKactivityCD16+,CD57+:variableNKactivityAssociatedwithpoorprognosisinnasallymphomasPositivestaining(normal):NKsubset,Tcellsubset(CD2,3,5),neuroectodermaltissue,brain,prostate,proximaltubulesofkidneyPositivestaining(tumors):neuroectodermaltumors,smallcelllungcancer(some),prostaticadenocarcinoma,nervesheathoriginlesions,metanephricadenoma,renalcarcinoidtumors,someclearcellrenalcellcarcinomas,spindlecellthymomas(AJSP2001;25:111,lymphomas(some)Microimages(AJSPsubscribers):metanephricadenoma(figure4C),Wilmstumor#1(figure5C),#2(figure6C),dendriticcellneurofibromawithpseudorosettesReference:AJSP2001;25:587,AJSP2001;25:1290 AkaLFA-3(lymphocytefunctionassociatedantigen);ligandforCD2MediatesadhesionbetweenNKandtargetcells,antigenpresentingcellsandTcells,thymocytesandthymicepithelialcellsPositivestaining(normal):leukocytes,erythrocytes,endothelialcells,epithelialcells,fibroblasts AkaprotectinRegulatescomplementmediatedcelllysisbyinhibitingformationofmembraneattackcomplex(MAC) GeneticdefectsthatcauseareductionorlossofbothCD59andCD55onerythrocytesproduceparoxysmalnocturnalhemoglobinuria(PNH)IncorporatedintoHIVenvelope,protectsvirusandHIVinfectedcellsagainstcomplementdepositionExpressiononerythrocytesimportantfortheirsurvivalPositivestaining(normal):mostcells Antibodiesprovidecostimulatory/comitogenicsignalsforTcells Positivestaining(normal):platelets,Tsubset,thymicepithelium,activatedkeratinocytes,synovialfibroblasts,glomeruli,smoothmusclecells,astrocytes GD3-carbohydratestructure 9-O-acetyl-GD3-carbohydratestructure 7-O-acetyl-GD3-carbohydratestructure AkaplateletglycoproteinIIb/IIIaReceptorforfibrinogen,fibronectin,prothrombin,thrombospondin,vitronectin,plasminogenMediatesplateletaggregationbybindingsolublefibrinogen,formingplateletplugDefectscauseGlanzmannthrombasthenia,anautosomalrecessivedisorderandthemostcommoninheritedplateletdiseasePositivestaining(normal):platelets,megakaryocytes,myeloidprogenitorcells,endothelialcellsPositivestaining(disease):AMLM7,AMLM6(some),blastsintransientmyeloproliferativedisorderNegativestaining:AMLM0-M5,M6(most)Microimages:megakaryoctyes(figuresC,D) AkaEselectin;endothelialleukocyteadhesionmolecule-1(ELAM-1)Ligandforsialyl-LewisXMediatesleukocyterollingonactivatedendotheliumatinflammatorysites,atherosclerosis,tumorcelladhesionduringhematogenousmetastasisPatientswithLeukocyteAdhesionDeficiency2syndrome,wholacksialylLewisXcomponentofselectincounter-receptors,sufferrecurrentpyogenicinfectionsPositivestaining(normal):endothelialcells(aftercytokinestimulation) AkaLselectin;LECAM-1Mediateslymphocytehomingtohighendothelialvenulesofperipherallymphoidtissue,leukocyterollingonactivatedendotheliumatinflammatorysitesPositivestaining(normal):B,T,NKcells,monocytes,neutrophils,eosinophils,precursorsReference:153240 AkaPselectin;PADGEMInteractionwithCD162mediatestetheringandrollingofleukocytesonthesurfaceofactivatedendothelialcells,thefirststepinleukocyteextravasationandmigrationMediatesrollingofplateletsonendothelialcells,platelet-mediateddeliveryoflymphocytestohighendothelialvenulesConstitutiveexpressionininflammationmaycontributetotissuedestruction,atherogenesisandthrombosisMaybereducedingrayplateletsyndrome,139090Redistributestotheplasmamembraneduringplateletactivationanddegranulation.Positivestaining(normal):platelets,megakaryocytes,activatedendothelialcells Akalysosomal-membrane-associatedglycoprotein3,LAMP-3,melanomaassociatedantigen,NKI-C3Intracellularlysosomal/endosomal/granuleprotein,inWeibel-PaladebodiesofvascularendotheliumMarkerofplateletactivation(transportedtosurfaceafteractivation)AssociatedwithearlystagesofmelanomaprogressionPositivestaining(normal):activatedplatelets,macrophages,fibroblasts,osteoclasts,endothelium,smoothmuscle,neuraltissue(brainwhitematterandperipheralnerves),synovialliningcellsPositivestaining(tumors):melanoma Importantinphagocytosisviareceptor-mediatedendocytosisofIgG-antigencomplexesMediatesantigencaptureforpresentationtoTcells,antibody-dependentcellularcytotoxicity,releaseofcytokinesandreactiveoxygenintermediatesPositivestaining(normal):Macrophages/monocytes,activatedgranulocytes,dendriticcells,earlymyeloidcellsPositivestaining(disease):AMLM0-M2(variable);M3(usually);M4,M5Negativestaining:AMLM7 AkaVIM2,ceramide-dodecasaccharideAdhesivemoleculethatappearstobesignificantriskfactorforextravascularAMLinfiltrationPositivestaining(normal):myeloidcells,monocytes Widelyusedforacuteleukemiacelltypingandtoidentifyasubsetofpre-pre-BALLAkasialylated-CD65MayinhibitphagocytosisPositivestaining(normal):granulocytes,monocytesPositivestaining(disease):myeloidleukemiacells AkaCEACAM1,biliaryglycoprotein,BGP,C-CAMPrimordialproteinofcarcinoembryonicantigen(CEA)familyCelladhesionmoleculecapableofactivatingneutrophils;mayregulateCD11/CD18activityReceptorforNeisseriagonorrheaandN.meningitidisDownregulatedincolorectal,endometrialandhepatocellularcarcinomas;supplementationmaycausetumorregressioninvitroorinrodentsDownregulatedinGleasongrade4/5prostatecarcinoma,HumPath2002;33:290Positivestaining(normal):granulocytes,epithelialcells,prostateglandsandducts(dense),bilecanaliculibetweenlivercellsPositivestaining(disease):lowgradeprostaticcarcinomaNegativestaining:prostatecarcinoma,Gleasongrade4/5Microimages(HumPathsubscribers):Prostate:A-normal,B-Gleasongrade3,C-Gleasongrade4,normalliver(figureF) AkaCEAgenemember6;formerlyCD67Capableofactivatingneutrophils;mayregulateCD11/CD18adhesionactivity Akanoncrossreactiveantigen(NCA)Capableofactivatingneutrophils;mayregulateCD11/CD18adhesionactivityPositivestaining(normal):granulocytes CapableofactivatingneutrophilsandfunctionsasareceptorforNeisseriagonorrheaandN.meningitidisMayplayasignalingroleandregulateadhesionactivityofCD11/CD18inneutrophilsPositivestaining(normal):granulocytes AkaCEA,carcinoembryonicantigenMayplayaroleintheprocessofmetastasisofcancercellsSerummarkeroftumorburden,relapseRemovedbyhepaticKupffercellsviaaspecificreceptor.Uses:85%sensitive,96%specificforlungadenocarcinomasvs.mesotheliomas;diffusecylasmicstainingwithmembraneenhancementPositivestaining(normal):biliarytract,colon(fetal),epithelialcells(apicalsurfaces),GIadenocarcinomas(endodermallyderived),granulocytes,smallintestinalcrypts;smallintestinalgobletcellmucin(notintracylasmic)Positivestaining(tumors):colonicandlungadenocarcinoma,medullarythyroidcarcinomaVariablestaining:breastcarcinoma,endometrialcarcinoma,neuroendocrinecarcinoma,urothelialcarcinomaNegativestaining:hepatocellularcarcinoma,mesothelioma,ovariancarcinoma,prostateadenocarcinoma,renalcellcarcinoma,thyroidcarcinomaotherthanmedullary Akapregnancy-specificglycoproteinMaybeinvolvedinimmuneregulation,protectionoffetusfrommaternalimmunesystemLowlevelsinmaternalbloodpredictspontaneousabortionPositivestaining(normal):syncytiotrophoblasts,fetalliver,myeloidcelllinesReference:176390 Recognizesnon-specificcross-reactiveantigenspresentongranulocytesMayhaveroleinneutrophilactivation AkaKP-1MayhaveroleinmacrophagephagocyticactivitiesSpecifictolysosomes,notcelllineagePositivestaining(normal):macrophage/monocytes,basophils,dendriticcells,mastcells,myeloidcells,CD34+progenitorcells,neutrophils,osteoclasts,activatedplatelets,BandTcellsPositivestaining(tumors):AML-M4/M5,angiosarcoma(granularcelltype),Bcelllymphoma(some),giantcellangioblastoma,granularcelltumors,hairycellleukemia,histiocyticsarcoma,interdigitatingdendriticcellsarcoma(AJSP2002;26:530),Langerhanscellhistiocytosis,mastocytosis,mastcelldisease(alsopositivefortryptase,CD43,CD117),melanoma(some)Microimages:multinucleatedgiantcellinthyroidglandgiantcellgranuloma(figureC),plexiformfibrohistiocytictumor,Rosai-Dorfmandisease#1,#2-figureDMicroimages(AJSPsubscribers):histiocyticlymphoma(figureA),histiocyticsarcoma(figureA),giantcellangioblastoma#1(figure5D),#2(figure6D)Microimages(ModPathsubscribers):Kupffercellsinnormalliver,Kupffercellsinseverenon-alcoholicsteatohepatitis(figureB)Reference:AJSP2001;25:1372,AJSP2003;27:258,ModPath2002;15:699 Akaactivationinducermolecule(AIM),earlyactivationantigen(EA-1)EarliestinduciblecellsurfaceglycoproteinacquiredduringlymphoidactivationInvolvedinearlyeventsofTcell,NKcell,monocyteandplateletactivationAssociatedwithTh-1Tcelldifferentiationandassociatedcytokines(IL-2,TNF-alpha,interferon-gamma),HumPath2002;33:330HighlyexpressedonTcellsfrominflammatoryinfiltratesofrheumatoidarthritis,viralhepatitis,autoimmunethyroiddisorders;Positivestaining(normal):activatedTcells,Bcells,NKcells,neutrophils,eosinophils,epidermalLangerhanscellsPositivestaining(disease):Tcelllymphomas(angioimmunoblastic,Lennert’s,mycosisfungoides/Sezarysyndrome)Negativestaining:anaplasticlargecelllymphomaMicroimages(HumPathsubscribers):A-tonsil,B-peripheralTcelllymphomaNOS,C-anaplasticlargecelllymphoma(H&E,frozen,paraffin) AkaCD27ligandRoleinTcellactivation;inducesTcellproliferationandenhancesgenerationofcytolyticTcellsPositivestaining(normal):activatedB,TcellsPositivestaining(disease):Reed-Sternbergcells AkatransferrinreceptorPresentonactivelyproliferatingcells;essentialforirontransportintoproliferatingcells(benignandmalignant)FerrotransferrinbindsCD71atneutralpH,isinternalizedtoanacidicendosomalcompartmentIron-freeapotransferrinremainsboundtoCD71atpH5,isreturnedtocellsurface,wherepHrisesto7.4.AtneutralpH,apotransferrinlosesaffinityforreceptor,isreleasedintocirculation,allowinganewcycletobeginPositivestaining(normal):allproliferatingcellsplusironrequiringcells:reticulocytes,erythroidprecursors,capillaryendotheliuminbrainPositivestaining(disease):AMLM6,primaryeffusionlymphoma CellsurfaceproteinexpressedexclusivelyonBcells;maycontrolBcellproliferationAssociatedwithCD5Positivestaining(normal):BcellsPositivestaining(disease):hairycellleukemia Akaecto-5"-nucleotidase,PI-linkedCatalysesdephosphorylationofpurineandpyrimidineribo-anddeoxyribonucleosidemonophosphatestotheircorrespondingnucleosidesMediatescostimulatorysignalsinTcellactivation,lymphocyteadhesiontoendotheliumMaybelymphocytematurationmarkerHighlevelsarepoorprognosticfactorsinleukemia/lymphomasPositivestaining(normal):BandTcellsubset;endothelialcells,onfolliculardendriticcells,epithelialcellsPositivestaining(disease):acuteTcellleukemia,CLL,ALL GammachainantigenassociatedwithMHCclassIIantigenInsynthesisofclassIIantigensofMHC,newlysynthesizedalphaandbetachainsformstablecomplexwithgammachainsintheendoplasmicreticulum;thentransportedtoGolgi,wheregammachaindissociatesPositivestaining(normal):B-cells,activatedT-cells,macrophages,activatedendothelialandepithelialcells Akalactosamines;LN-1LigandforCD22InvolvedincelladhesionPositivestaining(normal):Bcells,Tcells,erythrocytesPositivestaining(disease):“popcorncells”oflymphocytepredominanceHodgkindiseaseMicroimages:lymphocytepredominanceHodgkindiseaseReference:Archives2002;126:862 Alpha-2,6-sialylatedlactosamines(formerlyCDw75andCDw76) Akaglobotriaosylceraminde,pKbloodgroupBindstoShigatoxin(producedbyShigelladysenteriae),verotoxin1(producedbyE.coli),CD19Positivestaining(normal):BcellsPositivestaining(disease):Burkitt"slymphoma EncodestheIg-alphaproteinoftheB-cellantigenreceptor;receptoralsoincludesIg-betaprotein,surfaceimmunoglobulinExpressedearlyinB-celldifferentiation(oftenpositivewhenmatureB-cellmarkersarenegative);alsoexpressedinplasmacellsUses:positiveinacutelymphoblasticleukemia,smallBcelllymphoproliferativedisorderswhenCD20maybenegative;moreconsistentlypreservedininfarctedlymphomasthanCD20,Archives2003;127:60Positivestaining:Bcelllymphomas,lymphocyte-predominantHodgkinlymphoma,classicHodgkinlymphomaMicroimages:Warthin-Finkeldeygiantcellsinmeaslesrelatedappendicitis(FigureC),infarctedlymphomas,figures2&6 EncodestheIg-betaproteinoftheB-cellantigenreceptor;receptoralsoincludesIg-alphaprotein,surfaceimmunoglobulin AkaB7-1,BB1LigandforTcellmarkerCD28orCTLA4(CD152)Co-regulatorofTcellactivationwithCD86Hascriticalroleinautoimmune,humoral,andtransplantresponsesPositivestaining(normal):activatedBcells,Tcells,macrophages,dendriticcellsReference:112203 AkaTargetofanAnti-ProliferativeAntibody(TAPA1)AntibodiesagainstTAPA1inducehomotypicaggregationofcellsandcaninhibittheirgrowthMemberofCD19/CD21/Leu-13signaltransductioncomplex;regulatescellgrowthinunknownmannerMaybesiteofbindingofHepatitisCvirusPositivestaining(normal):lymphocytes,endothelialcells,epithelialcellsNegativestaining:erythrocytes,platelets,neutrophils AkaprostatecancerantimetastasisgeneKAI1,"kangai"(Chineseforanticancer).Metastasissuppressorgene;downregulatedintumorprogressionofcancersExpressioncorrelateswithp53expressionAssociateswithCD4orCD8anddeliverscostimulatorysignalsforTcellreceptorpathwayActivationantigenforTcellsPositivestaining(normal):activated/differentiatedhemaoieticcellsNegativestaining:erythrocytesReference:600623 Summary:MarkerfordendriticcellsMayassistinantigenpresentationorcellularinteractionsthatfollowlymphocyteactivation.Positivestaining(normal):dendriticcells,Langerhanscells,lymphocytesPositivestaining(disease):Churg-Strausssyndromemyocarditisininflammatoryinfiltrates,Archives2003;127:98Microimages:Churg-StrausssyndromemyocarditisReference:GeneCards Summary:HomophilicadhesionmoleculethatenhancesIFN-gammasecretionPositivestaining(normal):Bcells,thymocytes,Tcellsubset,monocytes/macrophages,plateletsReference:GeneCards Summary:MarkerofplasmacellsandhairycellleukemiaAkaLILRB1 AlsoinhibitsBcellsactivatedbyantigenreceptorandmyelomonocyticcellsactivatedbyHLA-DRPositivestaining(normal):plasmacells(strong),mantlezone,germinalcenterBcells,Tcellsubset,NKcellsubset;dendriticcellsPositivestaining(disease):hairycellleukemia(strong)Reference:GeneCards CD85a-ILT5/LIR3CD85b-ILT8CD85c-LIR8CD85d-ILT4/LIR2,MIR10CD85e-ILT6/LIR4CD85f-ILT11CD85g-ILT7CD85h-ILT1/LIR7CD85i-LIR6CD85j-ILT2/LIR1,MIR7CD85k-ILT3/LIR5CD85l-ILT9CD85m-ILT10 Summary:CostimulatesIL-2productionandTcellproliferationAkaB7-2LigandforCD28(CD80alsobindsCD28),CD152(CTLA4)InductionofanimmuneresponserequiresTcellstoreceive2setsofsignalsfromantigenpresentingcells.ThefirstisdeliveredthroughtheT-cellreceptorcomplex,whilethesecondisprovidedbytheB-cellactivationantigensB7-1,orCD80andB7-2,orCD86byinteractionwiththeT-cellsurfacemoleculesCD28andCTLA4Positivestaining(normal):interdigitatingdendriticcellsinTzonesofsecondarylymphoidorgans,Langerhanscells,peripheralblooddendriticcells,memoryBcells,germinalcenterBcells,monocytes(higherlevelsafterg-IFN),endothelialcells,activatedTcellsReference:GeneCards Summary:Receptorforurokinaseplasminogenactivator(uPA),whichconvertsplasminogentoplasmin Implicatedinmetastasis-receptorsforuPAandplasminarefoundatleadingedgeoftumorcells;plasmincauseshydrolysisofextra-cellularmatrixproteinsinthepathofcellularinvasionMayhaveadherenceandchemotaxisfunctionsPositivestaining(normal):T-cells,NKcells,monocytes,neutrophils(higherafteractivation),endothelialcells,fibroblasts,smoothmusclecells,keratinocytes,placentaltrophoblasts,hepatocytesPositivestaining(tumors):carcinomasofbreast,colonandprostate;melanomaReference:GeneCards Summary:receptorforC5a,thechemotacticandinflammatorypeptideanaphylatoxinStimulateschemotaxis,granuleenzymereleaseandsuperoxideanionproductionReducedlevelsinHIVpatientsPositivestaining(normal):granulocytes,macrophages/monocytes,dendriticcells,astrocytes,microgliaReference:GeneCards Summary:IgAFcreceptor,bindsIgAandeliminatesIgAcoatedtargetsInducesphagocytosis,degranulation,respiratoryburstandkillingofmicroorganismsPositivestaining(normal):granulocytelineage,monocytelineage,activatedeosinophils,alveolarandsplenicmacrophages Summary:MaymediatedifferentiationofhemaoieticstemcellsandsynaptogenesisintheCNSAkaThy-1CD34+CD90+cellsincludehemaoieticstemcellsthatserveasautologousgraftstoreplacethebonemarrowinpatientswithmalignanciesPositivestaining(normal):hemaoieticstemcells,neurons,connectivetissue Summary:lowdensitylipoproteinreceptor-relatedprotein1;akaalpha-2-macroglobulinreceptorBindstoapoE-containinglipoproteinsandmediateschylomicronremnantclearancefromtheplasmaAlsoacellsurfacereceptorforheatshockproteins,Archives2003;127:178 MayregulatedendriticcellfunctionPositivestaining(normal):leukocytes,endothelialcells Positivestaining(normal):granulocytes,monocytes,endothelialcellsPositivestaining(disease):AMLblasts InhibitsNKcellfunctionPositivestaining(normal):NKcells,gamma/deltaandalpha/betaTcells Summary:activatesapoptosiswhenboundbyFasligand(FasL,CD178)AkaFAS,APO-1ReceptorforFasL;whenactivated,FADD(Fas-associateddeathdomain,aseparateproteinfromFas)recruitscaspase-8tothereceptor;resulting“death-inducingsignalingcomplex”performscaspase-8proteolyticactivation;activatedcaspase-8initiatesasubsequentcascadeofcaspasesmediatingapoptosisFas-FasLsystemmediatesextra-thymicself-tolerance(FasL+cellsinduceapoptosisininfiltratingFas+lymphocytes),Tcellmediatedcytotoxicity,haltingofimmuneresponseMutationscauselossofregulationofBlymphocytes,predisposingtosystemicautoimmunity(SLE);FasmutantmicedeveloplymphadenopathyandsystemicautoimmunediseaseDownregulationmaycausereductioninCD4+TcellsinHIV,Archives2002;126:28Positivestaining(normal):activatedBcells,activatedTcells(initiallyextrabutnonfunctionalFas),restingTcells(lowlevels),breast,vaginal,endometrialandovarianepitheliumPositivestaining(disease):thyroidepithelialcellsinHashimoto’sthyroiditis,Reed-SternbergcellsinclassicHodgkin’slymphoma,AJSP2001;25:388,Barrett’sesophagus,esophagealadenocarcinomaNegativestaining:normalgastricmucosaReferences:GeneCardsImages:Apoptosispathwaychart,FasexpressioninlymphnodesofHIVpatientsMicroimages(HumPathsubscribers):benigntamoxifen-exposedpostmenopausalendometrium AkaTcellactivatedincreasedlateexpression(TACTILE)MaybeinvolvedinadhesionofactivatedTandNKcellslateinimmuneresponsePositivestaining(normal):activatedTcells BindstoCD55andGprotein-coupledreceptorsMaybeinvolvedincelladhesionandsignalingprocessesearlyafterleukocyteactivationHighlyexpressedatsitesofinflammationinskin,lungandrheumatoidarthritis.Positivestaining(normal):activatedT>Bcells,monocytes/macrophages,dendriticcells,granulocytesPositivestaining(tumors):thyroidcarcinomas,GIadenocarcinomasNegativestaining:microglia Aminoacidtransporter,akaSLC3A2Associatedwithfunctionofpancreaticisletcells,thyroidCcellsandparathyroidcellsAlsoinvolvedinnormalandneoplasticcellgrowthUpregulatedonleukocytesininflammatorylesions,stronglyexpressedbyneoplasticcells.Positivestaining(normal):broadPositivestaining(tumors):transformedcells Summary:relativelynon-specificmarkerforEwing’ssarcomaandTcelllymphomaAkaMIC2,O13AssociatedwithEWS-FLI1fusiontranscript,t(11;22)(q24;q12),causingFLI-1proteinoverexpressionInterpretation:distinctmembranousstainingforEwings/PNET;cylasmicforothertumorsPositivestaining(normal):ovariangranulosacells,pancreaticislets,infantthymus,SertolicellsPositivestaining(tumors):Tcellacutelymphoblasticlymphoma,calcifyingaponeuroticfibroma,Ewing"ssarcoma/PNET(95%sensitive),gastrointestinalstromaltumor,intraabdominaldesmoplasticsmallroundcelltumor(23-35%),leukemiacutis,nuchalfibromas,perineuroma(myxoidsclerosingtype),rhabdomyosarcoma(membranousstaining,AJSP2002;26:1175),sinonasalundifferentiatedcarcinoma(rare,AJSP2001;25:156),smallcellcarcinomasoflung(rare),solitaryfibroustumor,synovialsarcoma(poorlydifferentiated,monophasicandmyxoidtypes),Wilm’stumors(some),endometrialstromaltumorswithsexcorddifferentiationNegativestaining:adultneuroblastomaMicroimages:GISTvs.solitaryfibroustumorMicroimages(AJSPsubscribers):PNETofpancreas(figureB),Ewingssarcoma/PNETofkidney#1,#2,sinonasalundifferentiatedcarcinomaMicroimages(HumPathsubscribers):EwingssarcomaofesophagusMicroimages(ModPathsubscribers):PNETofdura(figureC)Reference:Archives2002;126:1189,AJSP2002;26:1040,ModPath2002;15:673 CD100IncreasesCD45inducedTcelladhesion;down-regulatesBcellexpressionofCD23Positivestaining(normal):mosthemopoieticcells,increasedexpressionafterTcellactivationNegativestaining:immaturebonemarrowcells CD101Positivestaining(normal):monocytes,granulocytes,dendriticcells,activatedTlymphocytes CD102AkaICAM-2Providescostimulatorysignalinimmuneresponse;importantinlymphocyterecirculationPositivestaining(normal):restinglymphocytes,monocytes,platelets,vascularendothelialcellsPositivestaining(tumors):somelymphomasNegativestaining:neutrophils CD103Akahumanmucosallymphocyteantigen1,integrinalphaEchainUsefulmarkerforintraepitheliallymphocytes(normalortumoral),althoughalsoexpressedbyactivatedlymphocytesPositivestaining(normal):intraepitheliallymphocytes,somelaminapropriaTlymphocytesintheintestinePositivestaining(tumors):hairycellleukemia;AML(many),enteropathy-associatedTcelllymphomas,adultHTLV-1associatedTcellleukemia CD104Akaintegrinbeta4chainPositivestaining(normal):thymocytes CD105AkaendoglinRegulatorycomponentofTGF-betareceptorcomplex;mediatescellularresponsetoTGF-beta1TargetgeneforHereditaryHemorrhagicTelangiectasiatypeI;eachaffectedfamilyhasadifferentmutationPositivestaining(normal):activatedmonocytes,endothelialcells;erythroidprecursorsinmarrow;syncytiotrophoblasts,cytotrophoblastsinfirsttrimester(transientexpression) CD106AkaVCAM-1;alpha4beta1ligandAdhesionmolecularfoundinstimulatedendotheliumthatplaysaroleinmigrationofwhitebloo--CD107aAlsocalledlysosome-associatedmembraneprotein1(LAMP-1)EnclodesamembraneglycoproteinthatprovidesselectinswithcarbohydrateligandsMayplayaroleintumormetastasis,ashighlymetastatictumorcellsexpressmorelampmoleculesontheircellsurfacePresentinlysosomes,degranulatedplatelets,activatedneutrophils,TcellsandendotheliumReferences:(OMIM)-153330CD107bAlsocalledlysosome-associatedmembraneprotein2(LAMP-2)EnclodesamembraneglycoproteinthatprovidesselectinswithcarbohydrateligandsMayplayaroleintumormetastasis,ashighlymetastatictumorcellsexpressmorelampmoleculesontheircellsurfaceMayprotectormaintainlysosomesDefectscausevariousglycogenstoragediseasesPresentinlysosomes,degranulatedplatelets,weaklyinactivatedneutrophilsandendotheliumReferences:(OMIM)-309060CD108AlsocalledSEMA7A,John-Milton-Hagen(JMH)humanbloodgroupantigenAsemaphorinPotentstimulatorofcytokineproduction,chemotaxisandsuperoxidereleaseinmonocytes;mayhaveadhesionfunction;maymodulateimmuneresponseAutoantibodiesarecommon,andassociatedwithlossofJMHantigenexpressionDeficiencymaybeassociatedwitharareformofcongenitaldyserythropoieticanemiaExpressedonerythrocytes,lymphoblasts,lymphocytes(lowlevels)CD109Glycophosphatidylinositol-linkedglycoproteinCarriesthebiallelicplatelet-specificGovantigensystem,implicatedinrefractorinesstoplatelettransfusion,neonatalalloimmunethrombocyenia,andposttransfusionpurpuraExpressedonsubsetofhemaoieticstemandprogenitorcellsandonactivatedplateletsandTcells CD110Akathrombopoietinreceptor(TPO-R),myeloproliferativeleukemiavirusoncogene(MPL)BindingtothrombopoietininducesmegakaryocyteproliferationanddifferentiationandpreventsapoptosisMutationsfoundinsomepatientswithcongenitalamegakaryocyticthrombocyenia,adiseasecharacterizedbyseverecongenitalthrombocyeniawithvariablebleedingtendencyandabsenceofmegakaryocytesinthebonemarrowPositivestaining(normal):hemopoieticstemandprogenitorcells,megakaryocytesandprogenitors,platelets CD111Akapoliovirusreceptorrelated1(PRR1),nectin1Widelyexpressedadhesionmoleculethatisacomponentoftheadherensjunction;receptorforherpessimplexviruses1and2Positivestaining(normal):cellsfrommyeloid,monocyte,megakaryocytesanderythroidlineage,epithelialcells,neurons,endothelium CD112Akapoliovirusreceptorrelated2(PRR2)Adhesionmoleculethatisacomponentoftheadherensjunction;receptorforherpessimplexvirusPositivestaining(normal):cellsfrommyeloid,monocyte,megakaryocyteslineage,epithelialcells,neurons,endothelium CD113Reservedforfutureuse CD114Akagranulocytecolony-stimulatingfactorreceptor,G-CSFRSpecificregulatorofmyeloidproliferationanddifferentiationMutationspresentinsomepatientswithseverecongenitalneutropeniaPositivestaining(normal):granulocytes(all),monocytes,platelets,endothelium,placenta,trophoblasticcellsPositivestaining(tumors):culturedtumorcellsNegativestaining:eosinophils,lymphocytes,erythrocytes CD115Akac-fms,receptorformacrophagecolonystimulatingfactor,CSF-1RLocalizedoncylasmicmembrane;mediatesbiologicactivityofCSF-1v-fmsisaviraloncogenepresentinthefelineMcDonoughsarcomavirus(hasseveralsubstitutemutations)Relatedtoplateletderivedgrowthfactorreceptor,c-kit,vascularendothelialgrowthfactorreceptor,fibroblastgrowthfactorreceptor,highaffinitynervegrowthfactor(TrkA)Deficiencycausesreducedosteoclastsandmacrophages,abnormalboneremodelingandosteopetrosis,abnormalbreastdevelopmentanddecreasedfertilityPositivestaining(normal):macrophagesandprecursors,osteoclasts,placentaltrophoblast,breasttissue,microglia,neurons,astrocytesPositivestaining(tumors):10%AML,someendometrial,ovarianandbreastcancers,vascularsmoothmusclecellsinatheromas,choriocarcinomacells CD116GM-CSFreceptoralphachainPrimarybindingsubunitofGM-CSFreceptorPositivestaining(normal):monocytes,neutrophils,eosinophils,fibroblasts,endothelialcells,dendriticcells CD117Summary:proto-oncogeneactivatedinGISTtumorsAkac-kit,stemcellfactorreceptorGeneat4q11-21Receptorforkitprotein,a145kDtyrosinekinasegrowthfactorreceptorproteinimportantfordevelopmentandsurvivalofmastcells,hemopoieticstemcells,melanocytes,germcells,interstitialcellsofCajalHasactivatingorgainoffunctionmutationsinmostGISTtumors,oftenatexon11,lessoftenatexons9and13,HumPath2002;33:484Molecularimages(HumPathsubscribers):image1Kitsignalingpathways(HumPathsubscribers):chart1Tyrosinekinaseactivityofc-kitinGISTandbcl-abloverexpressioninCMLareinhibitedbyimatinibmesylate(Gleevec,STI571),atyrosinekinaseinhibitorusedtotreatthesediseases,HumPath2002;33:466Uses:confirmingdiagnosisofGIST(butseeotherCD117+tumorsbelow),possiblyconfirmchronicintestinalpseudo-obstruction,AJSP2003;27:228Interpretation:shouldbestronganddiffusecylasmicstaining,likethepositivecontrolPositivestaining(normal):interstitialcellsofCajal,hemopoieticprogenitorcells,melanocytes,embryonic/fetalbrain,endothelium,gonads,mastcells,breastepithelium,germcellsPositivestaining(tumors):AML,angiomyolipoma(AJSP2002;26:493),angiosarcomas(50%),clearcellsarcoma,CML,epithelioidsarcoma,Ewingsarcoma,gastrointestinalautonomictumors,gastrointestinalstromaltumors(GIST),granulocyticsarcoma,Hodgkin’slymphoma(someReed-Sternbergcells),intraabdominalfibromatosis(dependsonantibodyused,AJSP2001;25:549),mastcelldisease(alsopositivefortryptase,CD43,CD68);melanoma,mesentericfibromatosis(variable,AJSP2002;26:1296),metanephricadenosarcoma(AJSP2001;25:1451),omentalmesenchymaltumor,osteosarcoma,rhabdomyosarcoma,sclerosingmesenteritis(variable),seminomas/dysgerminomas,smallcelllungcancer(HumPath2002;33:1182),synovialsarcoma(~10%,usuallycylasmicstaining),adenoidcysticcarcinomaofsalivarygland(strongstaining)Negativestaining:alveolarsoftpartsarcomas,desmoplasticsmallroundcelltumors,glomustumors,leiomyomas(retroperitoneal,colorectal),leiomyosarcomas,myxomas(cardiac),schwannomas(colorectal),smoothmuscletumorsofuncertainmalignantpotential,solitaryfibroustumorsMicroimages:rhabdomyosarcomaofpulmonarytrunk,GISTvs.solitaryfibroustumor,malignantstromaltumorofgallbladder(figure4),Microimages(AJSPsubscribers):GIST(siteunspecified),rectalGIST(figureA),metanephricadenosarcomaofkidney(stromaonly),normalsmallbowel(figure1A),normalcolon(figure2A),chronicintestinalpseudo-obstruction(figure3A),intraabdominalfibromatosis(variableresultswithdifferentantibodies)-#1,#2,pediatricsynovialsarcomas,pediatricosteosarcomas,pediatricEwing’s/PNETMicroimages(HumPathsubscribers):GIST#1,#2,#3,#4(figureA),smallcelllungcanceroflung(A:H&E,B:control-GIST,C:2+staining,D:1+staining)Microimages(ModPathsubscribers):GIST(figuresG,H),interstitialcellsofCajalinpatientwithmultipleGISTtumorsReferences:Archives2002;126:1189,AJSP2002;26:486 CD118Reservedforinterferonalpha/gammareceptor CDw119InterferongammareceptorPositivestaining(normal):macrophages,Bcells CD120aAkaTNFR1,receptorfortumornecrosisfactoralphaandbeta,typeIReceptorbindingtoligandcausesapoptosis CD120bAkareceptorfortumornecrosisfactor(TNF)alphaandbeta,typeII CD121aAkaInterleukin1receptor(IL-1R)typeI,IL1-alphaInterleukin-1,aninflammatorymediator,consistsof2separatebutrelatedproteins,IL1-alphaandIL1-betaPositivestaining(normal):Tcells,thymocytes,fibroblasts,endothelialcells CDw121bAkaInterleukin1receptor(IL-1R)typeII,IL1-betaMayinhibitIL1activitybyactingasadecoytargetforIL1Positivestaining(normal):Bcells,macrophages CD122AkaInterleukin2receptorbetachain(IL-2Rbeta)CriticalcomponentofIL-2andIL-15-mediatedsignalingPositivestaining(normal):NKcells,Bcells,Tcells,monocytes CD123AkaInterleukin3receptoralphasubunitAssociateswiththeGM-CSFreceptor(GMRbeta)Positivestaining(normal):plasmacytoidmonocytes(brightwithflowcytometry,AJSP2002;26:852) CD124AkaInterleukin4receptorReceptorsubunitforInterleukin-4and13Positivestaining(normal):matureBcells,Tcells;hemopoieticprecursors;fibroblasts,endothelialcells CDw125AkaInterleukin5receptoralphasubunitTherapeutictargetofeosinophilicinflammationinvolvedinbronchialasthmaPositivestaining(normal):eosinophils,activatedBcells,basophils CD126AkaInterleukin6receptorContinuousexpressionofIL-6andCD130,ligandsforCD126,causeshypergammaglobulinemia,glomeruloproliferativenephritisandlymphoidinfiltrationinsomeorgansDysregulatedstimulationmaycausemyelomaandplasmacytomaPositivestaining(normal):Tcells,monocytes,activatedBcells,hepatocytes CD127AkaInterleukin7receptorPositivestaining(normal):Bcellprecursors,mostTcells,monocytes CDw128aAkaInterleukin8receptoralphasubunit,CXCR1Chemokinereceptor,powerfulneutrophilchemotacticfactorPositivestaining(normal):neutrophils,basophils,Tcellsubset,monocytes,keratinocytes CDw128bAkaInterleukin8receptorbetasubunit,CXCR2Chemokinereceptor,powerfulneutrophilchemotacticfactor,particularlytositesofinflammationBindsmultipleCXCchemokinesincludingIL-8Positivestaining(normal):maturegranulocytes,projectionneurons,neuroendocrinecells(various)Positivestaining(tumors):carcinoids,atypicalcarcinoids,metastaticcarcinoids,pituitaryadenomas,pheochromocytomas,medullarycarcinomasNegativestaining:smallcellcarcinomaoflung/cervix,largecelllungneuroendocrinecarcinoma,Merkelcellcarcinoma,neuroblastoma,melanoma CD129ReservedforInterleukin9receptor CD130Akagp130Requiredfortransducingbiologicalactivitiesofinterleukin-6,interleukin-11,leukemiainhibitoryfactor,ciliaryneurotrophicfactor,oncostatinM,andcardiotrophin-1Inhuman,IL-6andoncostatinMdependentactivationofgp130areinvolvedinmultiplemyelomaPositivestaining(normal):almostallcelltypes(lowlevels) CDw131AkacommonbetasubunitDoesnotbindanycytokinebyitself,butisacomponentofthehighaffinityIL-3,GM-CSFandIL-5receptorsDefectiveCDw131isassociatedwithproteinalveolarproteinosisPositivestaining(normal):myeloid(earlyandmature),earlyBcells CD132Akacommoncytokinereceptorgammachain-receptorforIL-2,IL-4,IL-7,IL-9andIL-15MutationinhumanscausesX-linkedseverecombinedimmunodeficiency(noTcells,noNKcells)CD132isatargetmoleculeforgenetherapyforX-SCIDPositivestaining(normal):Tcells,Bcells,NKcells,monocytes/macrophages,neutrophils CD133Akaprominin-like1,AC133AlternativetoCD34inselectinghemopoieticstemandprogenitorcellsfortransplantationstudiesLocalizedtomicrovilliandotherplasmamembraneprotrusionsPositivestaining(normal):CD34brighthemopoieticstemandprogenitorcells,neuralandendothelialstemcells,otherprimitivecellssuchasretina,villousandextravillouscytotrophoblast,syncytiotrophoblastPositivestaining(tumors):retinoblastoma,hemangioblasts,developingepitheliumNegativestaining:adultepithelialtissue,villousstroma CD134Akatax-transcriptionallyactivatedglycoprotein1receptor,OX40antigen,lymphoidactivationantigen CD135AkaFMS-liketyrosinekinase3,flt3GrowthfactorreceptorforearlyhemopoieticprogenitorsPositivestaining(normal):multipotential,myelomonocytic,andprimitiveBcellprogenitorsPositivestaining(tumors):mostAML,ALLandCML CDw136Akamacrophagestimulatingproteinreceptor,mspreceptorMayregulateciliarybeatfrequencyinepithelialcellsPositivestaining(normal):skin,kidney,lung,liver,intestine,andcolon CDw137CostimulatorofTcellproliferationPositivestaining(normal):Tcells,especiallyCD45RAandCD45R0;alsoBcells,monocytes,epithelialcells CD138Akaheparansulfateproteoglycan,syndecan-1Mediatescelladhesion,growthfactors;associatedwithlatestageofBcelldifferentiationIntegralmembraneproteinisareceptorforextracellularmatrixLossofCD138expressionisassociatedwithtumoraggressivenessinsquamouscellcarcinoma(SCC)ofheadandneckandlarynx;levelsalsoreducedininvasiveSCCbutnotinSCC-insituInterpretation:membranousstainingPositivestaining(normal):Bcellprecursors,plasmacells,stratifiedsquamousepitheliumPositivestaining(tumors):keratoacanthoma,myeloma,primaryeffusionlymphoma,pyothoraxassociatedlymphomaNegativestaining:matureBcells,lymphomas(evenplasmacytoidlymphomas)Microimages:plasmacellsinRosai-DorfmandiseaseMicroimages(AJSPsubscribers):primaryeffusionlymphoma(figureC)Microimages(HumPathsubscribers):primaryeffusionlymphoma(figureE)Microimages(ModPathsubscribers):keratoacanthoma#1(figureB),#2(figureB),invasivesquamouscellcarcinomaReferences:ModPath2002;15:45;AJSP2002;26:1363 CD139Positivestaining(normal):Bcells,monocytes,granulocytes,erythrocytes(weak),dendriticcells,glomeruliNegativestaining:Tcells CD140aAkaalphaplateletderivedgrowthfactorreceptor CD140bAkabetaplateletderivedgrowthfactorreceptor CD141Akathrombomodulin75kDtransmembraneglycoproteinandcofactorforthethrombin-mediatedactivationofproteinCMarkerofmesotheliomas,endothelialcellsandcoagulationfactorImportantfibrinolyticinhibitor,asitdecreasestheactivationofplasminogentoplasminCriticalforactivationofproteinCandinitiationoftheproteinCanticoagulantpathwayPlasmaCD141levelsareassociatedwithendothelialdamageInterpretation:membranousstainingpattern,oftenfocal(cylasmicstainingmaybeartifactual)Uses:Mesotheliomavs.lungadenocarcinoma:64%sensitive,95%specificformesotheliomas,butmustexcludevasculature;oftenmembranousstainingofperipherywithisolatedpapilla;negativestaininginsarcomatoidmesotheliomas;consideredtohavea“secondary”roleasothermarkersarebetter,HumPath2002;33:953Urothelialcarcinomas(positive)vs.renalcell,prostate,endometrialorcoloniccarcinomas,AJSP2001;25:1380Squamouscellcarcinomas(positive),AJCP1998;110:385,AJSP2003;27:150Positivestaining(normal):endothelialcells,megakaryocytes,keratinocytes,mesothelialcells,monocytes,neutrophils,platelets,smoothmusclecells,syncytiotrophoblasts,synovialliningcells,urotheliumPositivestaining(tumors):mesothelioma(epithelioid),squamouscellcarcinomas,trophoblastictumors,urothelialcarcinomas,vasculartumors(includingangiosarcoma),synovialsarcoma(diffuselypositivein10%,AJSP2001;25:610)Negativestaining:adenocarcinomaofcolon,endometrium,kidney,lung(usually),prostate;sarcomatoidmesothelioma,Microimages(AJSPsubscribers):lungsquamouscellcarcinoma,lungadenocarcinoma,mesothelioma(figure1B) CD142AkacoagulationFactorIII,thromboplastin,tissuefactorMajorinitiatorofclottinginnormalhemostasisandmanythromboticdiseases,viacomplexwithfactorVIIaAlsobindszymogenfactorVII,theinactiveprecursorform;oncebound,avarietyofserineproteasesrapidlyactivatefactorVIItoVIIavialimitedproteolysisNormallyabsentfromallcellsindirectcontactwithplasmaPositivestaining(normal):epidermalkeratinocytes,glomerularepithelialcellsandvariousotherepithelia,adventitialcellsofbloodvessels,astrocytes,myocardium,Schwanncells,stromalcellsofliver,pancreas,spleenandthyroid CD143Akaangiotensin-convertingenzyme,ACE,peptidyldipeptidaseAInvolvedinmetabolismofangiotensinIIandbradykinin;alsocleavessubstancePandLH-RHPatientswithhighactivityhaveDDgenotype,associatedwithMI,strokes,diabeticnephropathyNecessaryforspermatozoatobindtoeggandassociatedwithbetterpenetrationofeggPositivestaining(normal):endothelialcellsofsmall/mediumarteries,lungcapillaryendothelium,proximalrenaltubulebrushborders,basalganglianeuropil,granulosacells,Leydigcells,variableonothercells CD144Endothelial-specificcadherinlocalizedatintercellularjunctionsAkavascularendothelial-cadherinprecursor,VE-cadherin,cadherin5Cadherinsarecelladhesionproteinsthatpreferentiallyinteractwiththemselvesinahomophilicmannerinconnectingcells,thuscontributingtothesortingofheterogeneouscelltypesPositivestaining(normal):endothelialcells,brain CDw145Noinformationavailable CD146Akamelanomacelladhesionmolecule(MEL-CAM),cellsurfaceglycoproteinMUC18MaybeaneuralcrestcelladhesionmoleculeduringembryogenesisAssociatedwithtumorprogressionandthedevelopmentofmetastasisinhumanmalignantmelanomaSensitivebutnonspecificmarkerofdesmoplastic/spindlecellmelanoma;useifsuggestivehistology,S100positive,melanomamarkersotherwisenegative,AJSP2001;25:58Interpretation:expressionismembranousPositivestaining(normal):vascularsmoothmuscle,endothelium,intermediatetrophoblastinexaggeratedplacentalsitesandplacentalsitetrophoblastictumors(HumPath1999;30:687),subpopulationofTcells,endothelium,smoothmuscle,SchwanncellsPositivestaining(tumors):clearcellsarcoma(90%),leiomyosarcomas(almostall),melanoma(desmoplastic-84%,epithelioidmelanomas-100%,advancedprimarytumorsandmetastatictumors),melanoticschwannoma(100%),MPNST(27%),neurofibroma(40%),prostaticadenocarcinomaandhighgradePIN,squamouscellcarcinomas(some),vascularsarcomas(almostall)Negativestaining:normalmelanocytes,melanocyticnevi,cellularbluenevus,thinprimarymelanomas,placentalsitenodules(orfocal),epithelioidtrophoblastictumors(orfocal),cytotrophoblast,atypicalfibroxanthomaMicroimages(AJSPsubscribers):desmoplasticmelanoma(figure1D),clearcellsarcoma(figure3C),melanoticschwannoma(figure4C)Reference:AJSP2001;25:58 CD147Akaneurothelin,extracellularmatrixmetalloproteinaseinducerPositivestaining(normal):allleukocytes,redbloodcells,plateletsandendothelialcells CD148AkaHPTP-etaMaybeinvolvedincontactinhibitionofcellgrowthPositivestaining(normal):granulocytes,monocytes,memoryTcells,dendriticcells,platelets,fibroblasts,neurons,Kupffercells CDw149Deleted(nowdesignatedCD47R)atthe7thHLDAWorkshopReference:TissueAntigens2000;56:258 CD150Akasignallymphocyteactivationmolecule(SLAM)CostimulatorymoleculeonBlymphocytesanddendriticcellsPositivestaining(normal):thymocytes,CD45ROpositivesubpopulationofTcells,Bcells,dendriticcells,endothelium CD151MaymodifyintegrinfunctionorsignalingPositivestaining(normal):endothelium,platelets,megakaryocytes,epithelium CD152AkacytotoxicTlymphocyte-associatedprotein-4,CTLA4NegativeregulatorofTcellactivationCTLA4restrictionfragmentlengthpolymorphismsarelinkedtovariousautoimmunedisordersSharessequencehomologywithCD28;alsosharesligandsCD80andCD86withCD28Positivestaining(normal):activatedbutnotrestingTcells,activatedBcellsReferences:123890 CD153AkaCD30ligandEnhancesCD3-activatedTlymphocyteproliferation CD154AkaCD40ligand,CD40L,TNF-relatedactivationprotein(TRAP)RegulatesBcellfunctionbyengagingCD40DefectivegenepreventsimmunoglobulinclassswitchandisassociatedwithhyperIgMsyndrome,autoimmunehematologicdisorders,disorganizednodalfolliculararchitectureandPAS-positiveplasmacytoidcellscontainingIgM,lymphnodeswithoutgerminalcenters,shortenedLifespan,oftenwithgastrointestinalcancers(cholangiocarcinoma,hepatocellularcarcinoma,andadenocarcinoma)andCryptosporidiumparvuminfectionPositivestaining(normal):Tcells CD155AkapoliovirusreceptorInvolvedinintercellularadhesionPositivestaining(normal):embryonicstructuresgivingrisetospinalcordanteriorhornmotorneurons CD156aAkaADAM8MayplayaroleinmuscledifferentiationPossibleroleinneutrophilicextravasationPositivestaining(normal):neutrophils,monocytes CD156bAkaTumornecrosisfactorAlphaConvertingEnzyme(TACE),ADAM17Adhesionstructure;releasessolubleformsoftumornecrosisfactorandtransforminggrowthfactor-alphafromcellsPositivestaining(normal):allcellsexamined,withpro-domainremoved CD157AkaBonemarrowSTromalcellantigen1(BST1)Facilitatespre-B-cellgrowth33%homologytoCD38OverexpressionmaycausepolyclonalB-cellabnormalitiesinrheumatoidarthritisPositivestaining(normal):granulocytes,monocytes,Bcellprogenitors,Tcellsubpopulations CD158MemberofKIR(killercellimmunoglobulinlikereceptor)family,alsocalledkillercellinhibitoryreceptorsBindingbyHLAclassImoleculescausesinhibitionofNKorTcellcytotoxicactivityMelanomaspecificcytotoxicTlymphocytesmayexpressKIRandregulatetheirABIlitytokillthesetumorsPositivestaining(normal):Naturalkillercells(NKcells),someTcells CD158aAkaKIR2DL1/p58.1RegulatesNKcellmediatedcytolyticactivityIncludestwodifferentmoleculeswithinhibitoryandactivationeffects,presumablyencodedbydifferentgenesofthesamefamilyPositivestaining(normal):NKcellsubset CD158bCD158b1akaKIR2DL2/p58.2CD158b2akaKIR2DL3/p58.3RegulatesNKcellmediatedcytolyticactivityIncludestwodifferentmoleculeswithinhibitoryandactivationeffects,presumablyencodedbydifferentgenesofthesamefamilyPositivestaining(normal):NKcellsubset,rareTcellsCD158c-KIR2DS6/KIRXCD158d-KIR2DL4CD158e1-KIR3DL1/p70CD158e2-KIR3DS1/p70CD158f-KIR2DL5CD158g-KIR2DS5CD158h-KIR2DS1/p50.1CD158i-KIR2DS4/p50.3CD158j-KIR2DS2/p50.2CD158k-KIR3DL2/p140CD158z-KIR3DL7/KIRC1 CD159aAkaNKG2A,killercelllectin-likereceptorsubfamilyCmember1MediatessignalinginthekillingprocessbyNKcellsPositivestaining(normal):NKcells CD160 AkaBY55 ExpressiontightlyassociatedwithperipheralbloodNKcellsandCD8+Tlymphocyteswithcytolyticeffectoractivity Positivestaining(normal):circulatingNK(CD56dim,CD116+)andTcells,spleen,smallintestinalintraepitheliallymphocytes CD161Akakillercelllectin-likereceptorsubfamilyB,member1MaymediateNKcellfunctionPositivestaining(normal):NKcells,subsetofCD4+andCD8+Tcells,memoryTcells,thymocytes(some) CD162AkaP-SelectinGlycoproteinLigand1,PSGL-1ImportantinadhesiveinteractionsbetweencirculatingleukocytesandplateletsandendothelialcellsMediatesrollingonactivatedendotheliumoractivatedplatelets(whichexpressPselectin/CD62P)andotherleukocytesatinflammatorysitesSiteofbindingofhumangranulocyteehrlichiosisbacteriaPositivestaining(normal):myeloidcells,stimulatedTcells CD162R Positivestaining(normal):NKcells CD163Hemoglobin/haptoglobinscavengerreceptorSolubleformattenuatesimmuneresponsePositivestaining(normal):monocytes/macrophages CD164AkaMUC-24,sialomucinMucin-likecellsurfaceglycoproteinthatfacilitatesadhesionofCD34+cells;regulateshemopoieticcellproliferation CD165InvolvedinadhesionbetweenthymocytesandthymicepithelialcellsPositivestaining(normal):immaturethymocytes,monocytes,platelets,CNSneurons,isletcells,Bowman’scapsuleofkidneyPositivestaining(tumors):manyT-acutelymphoblasticleukemias(ALL) CD166AkaActivatedLeukocyteCellAdhesionMolecule(ALCAM)Adhesionmolecule,bindstoCD6Involvedinneuronalneuriteextension,embryonichemopoiesis,embryonicangiogenesisPositivestaining(normal):neurons,activatedTcells,activatedmonocytes,epithelium,fibroblasts CD167aAkaDiscoidinDomainReceptor1,DDR1HashomologousregiontotheDicytosteliumdiscoideumproteindiscoidinIinextracellulardomainTyrosinekinasereceptor,maybeimportantincytoskeletalorganizationandtheabilitytoalignwithothercellsduringaggregationReceptortyrosinekinaseshelpcellscommunicatewiththeirmicroenvironmentandregulatecellgrowth,differentiationandmetabolism.ActivatedbycollagentypesI-V,VIIIMayhavearoleintumorinvasionandmetastasisPositivestaining(normal):epithelialcells(breast,kidney,lung,GI,brain)Positivestaining(tumors):carcinomas(various) CD168AkaReceptorforHyaluronicAcid-MediatedMotility(RHAMM)BindingtohyaluronstimulatesciliarybeatingAlsohasroleincellsignaling,migrationandadhesionPositivestaining(normal):bronchialepithelium,CNSneurons CD169AkasialoadhesinMacrophage-restrictedcellularinteractionmoleculethatbindssialylatedligandsHighlyexpressedonmacrophagesinchronicallyinflamedtissues,suchasrheumatoidsynoviumandatheroscleroticplaquesPositivestaining(normal):macrophages(allsitesbutmicroglia)Negativestaining:microglia CD170AkaSialicacidbindingIG-likeLECtin5(SIGLEC5)Mayfunctionincell-cellinteractionPositivestaining(normal):neutrophils CD171AkaL1AdhesionmoleculerequiredfornormalneurohistogenesisMutationscauseCRASH(Corpuscallosumhypoplasia/agenesis,Retardation,Aphasia,Spasticparaplegia/shufflinggaitandHydrocephalusduetostenosisofaqueductofSylvius),anXlinkedneurologicdisorderMaymediatekidneybranchingmorphogenesis,maintenanceoflymphnodearchitectureduringimmuneresponse,co-stimulationofT-cellactivationinvitroPositivestaining(normal):post-mitoticneurons,glia,epithelialcells(some),lymphoidcells(some),myeloid(some),monocytes CD172aAkaSIRPalphaAdhesionstructure CD173AkabloodgroupH2MarkerofearlyhemaoiesisPositivestaining(normal):CD34+hemopoieticprogenitorcellsNegativestaining:maturelymphocytes CD174AkaLewisYantigenMarkerofearlyhemaoiesisPositivestaining(normal):CD34+hemopoieticprogenitorcellsNegativestaining:maturelymphocytes CD175AkaTnSimplemucin-typecarbohydrateantigenproducedintheinitialstepsofmucinbiosyntheticpathway,duetoaberrantorincompleteglycosylationofmucins CD175sAka CD176AkaThomsen-Friedenreich(TF)oncofetalbloodgroupantigen,galactosebeta1-3N-acetylgalactosaminealphaOccursincoloncancerandcolitis CD177AkaNB1glycoproteinMajorimmunogenicmoleculeofneutrophilmembranePositivestaining(normal):myeloidcells CD178AkaCD95ligand,Fasligand(FasL)ImportantroleinTcellmediatedcytotoxicity;inducesapoptosisinFas-expressingtargetcellsCellsinimmuneprivilegedsites(testis,anteriorchamberofeye,placenta)constitutivelyexpressFasL,whichinducesapoptosisinFas-expressinginfiltratingTcells,minimizinginflammatoryresponsesthatmightdamageimportantphysiologicfunctionsatthesesitesMayinfluenceinteractionoftumorcellswithhostimmunesystem;theoryisthatFasL+tumorcellsinduceapoptosisininfiltratingFas+mononuclearcellsFas-FasLbindingtriggersapoptosisinlymphocytesMutationsmayberelatedtosomecasesofSystemicLupusErythematosis(SLE)Processedbymetalloproteaseswhichcausesheddingofextracellularportionintoblood(sFasL)Positivestaining(normal):activatedandcytotoxicTcells,testis,anteriorchamberofeye,placenta;alsoSertolicells,neurons,thyroidepithelialcellsPositivestaining(tumors):Reed-SternbergcellsofHodgkin’slymphoma(nodularsclerosisandmixedcellularity,AJSP2001;25:388)Microimages(HumPathsubscribers):benigntamoxifen-exposedpostmenopausalendometrium CD179aAkaVpreB1Associatesnon-covalentlywithCD179btoformsurrogatelightchainascomponentofpreBcellreceptor,whichplaysacriticalroleinearlyBcelldifferentiationPositivestaining(normal):preBcells CD179bAkalambda-5Associatesnon-covalentlywithCD179atoformsurrogatelightchainascomponentofpreBcellreceptor,whichplaysacriticalroleinearlyBcelldifferentiationMutationsimpairBcelldevelopmentandcauseagammaglobulinemiaPositivestaining(normal):preBcells CD180AkaRP105RegulatesBcellrecognitionoflipopolysaccharide,amembraneconstituentofgram-negativebacteriaPositivestaining(normal):mantlezoneandmarginalzoneBcells(strong),otherBcells(weak/negative);peripheralbloodmonocytes,dendriticcells CD181Noinformationavailable CD182Noinformationavailable CD183AkaCXCR3 Receptorforsomechemokines;bindingofchemokinestoCD183inducesintegrinactivation,cytoskeletalchangesandchemotacticmigrationininflammation-associatedeffectorTcellsCD183+Tcellsdetectedininflamedtissuesofpatientswithjuvenilerheumatoidarthritis,multiplesclerosis,sarcoidosis,hepatitisCPositivestaining(normal):Tcellsininflamedtissue,eosinophils,plasmacytoiddendriticcells,hemopoieticprogenitorsNegativestaining:naïveTcellsinperipheralblood CD184AkaCXCR4,StromalcellDerivedFactor1(SDF1)ReceptorfortheCXCchemokineSDF-1AlsomajorHIV/SIVco-receptor(withCCR5/CD195)InvolvedinBcelldevelopment,myelopoiesis,cardiacventricularseptumformation,bloodvesselformationinGItract,cerebellargranularcelldevelopmentPositivestaining(normal):allmaturebloodcells,bloodprogenitorcells,endothelialandepithelialcells,astrocytes,neurons CD185Noinformationavailable CD186Noinformationavailable CD187Noinformationavailable CD188Noinformationavailable CD189Noinformationavailable CD190Noinformationavailable CD191Noinformationavailable CD192Noinformationavailable CD193Noinformationavailable CD194Noinformationavailable CD195AkaCCR5MacrophagesurfacereceptorandattachmentsiteforHIVandSIV,withCXCR4(CD184);workswithCD4ReceptorforCD8chemokinesRANTES,MIP1-alphaandMIP1-beta. CD196Noinformationavailable CDw197AkaCCR7 CD198Noinformationavailable CD199Noinformationavailable CD200AkaOX2AnimmunoadhesinthatmaydeliverimmunosuppressivesignalsandregulateautoimmunedisordersInhibitoryformacrophagelineagecellsPositivestaining(normal):folliculardendriticcells,thymocytes,Bcells,Tcells,neurons,kidneyglomeruli,syncytiotrophoblast,endothelialcells CD201BindsproteinCinacalcium-dependentmannerAkaEndothelialProteinCReceptor(EPCR),proteinCreceptorProteinCisavitaminKdependentenzymewithmajorroleincoagulationofblood;activatedwhenthrombinbindstothrombomodulinonendothelium.MutationsinCD201andthrombomodulinassociatedwithlatefetalloss;similarmutationassociatedwithvenousthromboembolismandmyocardialinfarctionPositivestaining(normal):endothelialcells(notinliverandkidney) CD202bAkaTie2(TyrosinekinasewithIg-likeloopsandEpidermalgrowthfactorhomologydomains),akaTekReceptortyrosinekinaseat#9p21,bindstoangiopoietin-1MaybeearliestmammalianendothelialcelllineagemarkerInvolvedinveinmorphogenesisandcommunicationbetweenendothelialandsmoothmusclecellsforremodelingandrepairofbloodvesselsDefectsassociatedwithinheritedvenousmalformationsPositivestaining(normal):endothelialcells,hemopoieticcells CD203cAkaE-NPP3/PDNP3Enzymethatcatalyzeshydrolysisofoligonucleotides,nucleosidephosphates,andNADPositivestaining(normal):prostate,uterus,basophils,mastcells,gliomas,myeloidcells CD204Akamacrophagescavengerreceptor1PlaysaroleinendocytosisofmacromoleculesPositivestaining(normal):myeloidcells CD205AkaDEC205Possibleantigen-uptakereceptorwitharoleininitiatingimmuneresponsePositivestaining(normal):dendriticcells CD206AkamacrophagemannosereceptorActsinphagocytosisandpinocytosisofmannose-containingsolutesPositivestaining(normal):dendriticcells CD207Akalangerin(Langerhanscellspecificc-typelectin)FunctionsasendocyticreceptorLocalizedtoBirbeckgranulesMannosebindingtothisproteinmaycauseantigeninternalizationintoBirbeckgranulesandaccesstoanonclassicalantigen-processingpathwayPositivestaining(normal):Langerhanscells(immaturedendriticcellsofepidermisandmucosa) CD208DendriticcellLAMP(DC-Lamp)IndicatesdendriticcellmaturationPositivestaining(normal):dendriticcells CD209AkaDC-SignBindstoHIV1gp120MediatestransientadhesionofdendriticcellswithTcellsPositivestaining(normal):dendriticcells CDw210AkaIL-10receptorInterleukin-10(124092)producedbyBcells,Thelpercells,andmonocyte/macrophages,exhibitsdiverseactivitiesondifferentcelllinesIL10inhibitsmacrophageactivationbyinterferon-gammaPositivestaining(normal):monocytes,BandTcells,largegranularlymphocytes,spleen,thymus,placenta,lung,liver CD211Noinformationavailable CD212AkaIL-12receptorInterleukin-12promotescell-mediatedimmunitytointracellularpathogensbyinducingtype1helperTcellresponsesandinterferon-gammaproduction.LackofIL12associatedwithsevere,idiopathicmycobacterialandSalmonellainfections,maturegranulomasPositivestaining(normal):Tcells,NKcells CD213a1AkaIL-13receptor,alpha1BindsIL-13withlowaffinityWithIL-4r-alpha,canformafunctionalreceptorforIL-13Positivestaining(normal):ubiquitous,B-cells,T-cellsandendothelialcells,highestlevelsinheart,liver,skeletalmuscleandovary CD213a2AkaIL-13receptor,alpha2Inhibitsbindingofinterleukin-13totheIL13cellsurfacereceptorPositivestaining(normal):placenta CD214Noinformationavailable CD215Noinformationavailable CD216Noinformationavailable CDw217AkaIL17receptorCytokinethatisinducedinactivatedCD4+TcellsIL17inducesstromalcellstoproduceproinflammatoryandhemopoieticcytokines;enhancesexpressioninfibroblastsofICAM-1 CD218Noinformationavailable CD219Noinformationavailable CD220Akainsulinreceptor CD221Akainsulin-likegrowthfactor1receptorMediatesinsulinstimulatedDNAsynthesisandIGF1stimulatedcellproliferationanddifferentiationOftenoverexpressedinmalignanttissue,whereitfunctionsasananti-apoptoticagentbyenhancingcellsurvival CD222Akainsulin-likegrowthfactor2receptor,mannose6phosphatereceptorAlsoareceptorforlysosomalhydrolases(i.e.assistsinsortinglysosomalenzymesfromGolgiapparatusorextracellularspacetolysosomes) CD223AkaLymphocyte-ActivationGene3(LAG-3)HomologoustoCD4AssociateswithMHCclassIImoleculesonmonocytes/dendriticcells,whicharesubsequentlyactivatedMayhelpactivatedCD4+andCD8+Tcellstofullyactivatemonocytesanddendriticcells,leadingtooptimizedMHCclassIandclassIITcellresponsesPositivestaining(normal):activatedTcells,activatedNKcells CD224Akagamma-glutamyltransferaseGeneat22q11.1-q11.2Catalyzesthetransferoftheglutamylmoietyofglutathionetoavarietyofaminoacidsanddipeptideacceptors,whichmaintainsahomeostaticbalanceregardingoxidativestress. CD225AkaLeu13,interferon-inducibletransmembraneprotein1Involvedinrelayingantiproliferativeandhomotypicadhesionsignals CD226AkaDNAM-1,PlateletandTcellActivationantigen1(PTA1)MediatesadhesiontoanunknownligandTcellexpressionincreasedinsomepatientswithautoimmunediseaseandviralinfectionPositivestaining(normal):NKcells,platelets,monocytes,subsetofBandTcellsNegativestaining:granulocytes,erythrocytes CD227AkaEMA,MUC1,episialinLargecellsurfacemucinglycoproteinexpressedbymostglandularandductalepithelialcellsandsomehemopoieticcellsHighlyexpressedbymostadenocarcinomas,associatedwithpoorprognosis,HumPath1995;26:432Shedintothebloodstreamofadenocarcinomapatients,usedincommercialserumtumormarkerassays(CA15-3)ExpressedbynearlyallcasesofPaget’sdisease,canusetoscreen/confirmpresenceofPaget’scellsinepidermis,AJSP2001;25:1469Associatedwithinvasioninpancreatictumors,AJSP2002;26:466Positivestaining(normal):apicalsurfaceofalmostallglandularandductalepithelialcellsincludingbreastandpancreas,activatedTcells,monocytes,someBcells,folliculardendriticcells,perineurialcellsPositivestaining(tumors):adenocarcinoma(most),anaplasticlargecelllymphoma,epithelioidsarcoma,meningioma,mesothelioma(some),myeloma,Paget’sdisease,plasmacytomaNegativestaining:hepatocellularandadrenalcarcinoma,germcelltumorMicroimages:synovialsarcomastainingofglandularstructures,urothelialcarcinoma-highgradeReferences:JLeukocBiol2002;72:692 CD228AkamelanotransferrinCell-surfaceglycoproteinfoundonmelanomacells,withsequencesimilarityandiron-bindingpropertiesoftransferrinsuperfamily CD229AkaLymphocyteantigen9MaybeinvolvedinadhesionbetweenTcellsandaccessorycells CD230Akaprionprotein(“PRoteinINfectiousagent”)MutationsassociatedwithGerstmann-Strausslerdisease,Creutzfeldt-Jakobdisease(CJD),familialfatalinsomnia,whichareneurodegenerativeconditionstransmissiblebyinoculationorinheritedasautosomaldominantdisordersAberrantisoformscanactasaninfectiousagentinthesedisordersaswellasinkuruandinscrapieinsheepReplication(infectivity)occursasabnormalproteinwithconformationalchangerecruitscellularprionandconvertsitintoinfectiveformwithsameconformationalchangePositivestaining(normal):neurons(nonpathogenicisoform)Reference:176640 CD231AkaTcellAcuteLymphoblasticLeukemiaAntigen-1(TALLA-1),TM4SF2,A15InvolvedinX-linkedmentalretardation,NatGenet2000;24:167Positivestaining(normal):brainneuronsPositivestaining(tumors):Tcellacutelymphoblasticleukemia,neuroblastomacellsNegativestaining:Bcells,monocytes CD232AkaVirusEncodedSemaphoringProteinReceptor(VESPR)Mayfunctionasanimmunemodulatorduringvirusinfection. CD233Akaband3Erythrocytemembraneproteinthatfunctionsasananion(chloride/bicarbonate)exchangerandattachmentsiteforCytoskeleton(wherespectrin/actinbindtomembranelipidbilayer)TruncatedformofCD233isexpressedinkidneyandinvolvedinacidsecretionMutationscausehereditaryspherocytosisordistalrenaltubularacidosis(duetodefectiveacidsecretion)OthermutationscausenovelbloodgroupantigenswhichformtheDiegobloodgroupsystemSoutheastAsianovalocytosisisduetoheterozygousdeletions,commonwherePlasmodiumfalciparummalariaisendemic,associatedwithabnormallyrigid,stomatocyticerythrocytes,asymptomatic;childrenareprotectedagainstcerebralmalariaPositivestaining(normal):erythrocyteplasmamembrane(strong),basolateralmembraneofa-intercalatedcellsofthedistaltubulesandcollectingductsofthekidneyNegativestaining:allothercells CD234AkaDuffybloodgroupantigen(Fyglycoprotein);erythrocytechemokinereceptor,DuffyAntigenReceptorforChemokines(DARC)RBCreceptorforPlasmodiumvivax,amalarialparasiteNegativityassociatedwithsicklecelltrait,duetocommonprotectionagainstmalariaprovidedbybothtraitsAfrican-AmericansoftenDuffynegativeandresistanttoP.vivaxmalariaPositivestaining(normal):endothelialcellsofpost-capillaryvenules,Purkinjecellsofcerebellum CD235a GlycophorinsAandBaremajorsialoglycoproteinsofthehumanerythrocytemembraneContainsantigenicdeterminantsfortheMNbloodgroupPositivestaining(normal):erythroidcells CD235b GlycophorinsAandBaremajorsialoglycoproteinsofthehumanerythrocytemembraneContainsantigenicdeterminantsfortheMNbloodgroupPositivestaining(normal):erythroidcells CD235ab Positivestaining(normal):erythroidcells CD236 Positivestaining(normal):erythroidcells CD236R Positivestaining(normal):erythroidcells CD237 CD238 Positivestaining(normal):erythroidcells CD239 Maymediatecell-cell,cell-matrixadhesion,signaltransductionPositivestaining(normal):erythroidcells CD240CE Positivestaining(normal):erythroidcells CD240D Positivestaining(normal):erythroidcells CD240DCE Positivestaining(normal):erythroidcells CD241AkaRh50a,RhantigenRhesusbloodgroup-associatedglycoprotein;playsroleintransportofantigentocellsurfaceofredbloodcellsPositivestaining(normal):erythroidcells CD242Akaintercellularadhesionmolecule4(ICAM-4),Landsteiner-WienerbloodgroupDiscoveredwithantibodyraisedinguineapigsinjectedwiththecellsofrhesusmonkeys,butRhdesignationhadalreadybeentaken CD243AkaMDR-1(multidrugresistancetocancer),PglycoproteinMemberoflargesuperfamilyofhighlyconservedATPbindingcassettetransportproteins"Detoxifyingagent"thatpumpstoxinsoutofcells,alsotransportssteroidhormonesPrognosticimportance:correlateswithpoorresponsetochemotherapy/shortersurvivalforosteosarcomaPositivestaining(normal):adrenalcortex,biliarycanaliculi,blood-brainendothelium,blood-testicleendothelium,placenta,GIendothelium,proximalrenaltubules,somebonemarrowstemcells CD244Aka2B4NKcellsurfacereceptor;regulatesNKandTcellfunction CD245Akap220/240 CD246Anaplasticlymphomakinasegeneat2p23;AlsocalledCD246Membranespanningtyrosinekinasereceptor,memberofinsulinreceptorfamilyLigandisgrowthfactorpleiotrophin3"endcontainscatalyticdomainoftyrosinekinaset(2;5)associatedwithTcellanaplasticlymphomaviafusionofALKandnucleophosminproteinHasimportantroleinbraindevelopment CD247Akazetachain,TcellreceptorzetaFormsTcell-CD3receptorcomplex,togetherwithTCRalpha/betaandgamma/deltaheterodimers,CD3-gamma,deltaandepsilonCouplesantigenrecognitiontoseveralintracellularsignal-transductionpathways;lowexpressionoftheantigenresultsinimpairedimmuneresponse.Positivestaining(normal):Tcells EndofCDmarkers100-247
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CD1
CD1a
CD1b
CD1c
CD1dPositivestaining(normal):thymus(lowlevels),bowel
CD1e
CD2
CD2RCD2epiesrestrictedtoactivatedTcellsPositivestaining:activatedTcells,?NKcells
CD3
CD4
CD5
CD6
CD7
CD8
CD9
CD10
CD11
CD11a
CD11b
CD11c
CD12
CD13
CD14
CD15
CD15s
CD15u
CD16a
CD16b
CD17
CD18
CD19
CD20
CD21
CD22
AkaBlymphocytecelladhesionmolecule(BL-CAM)
MaylocalizeBcellsinlymphoidtissues;bindsCD45
CD23
CD24
PromotesantigendependentproliferationofBcells;preventsdifferentiationintoplasmacells
CD25
CD26
CD27
CD28
CD29
CD30
CD31
CD32
CD33
CD34
CD35
CD36
CD37
Possiblyinvolvedinsignaltransduction,belongstotetraspaninfamily
CD38
CD39
CD40
CD41
CD42a
CD42b
CD42c
CD42d
CD43
CD44
CD44h
CD44r
CD45
CD45RO
CD46
CD47
CD47R
CD48
CD49a
CD49b
CD49c
CD49d
CD49e
Fibronectinandfibrinogenreceptor
CD49f
CD50
CD51
CD52
CD53
CD54
CD55
CD56
CD57
CD58
CD59
CDw60
ExpressedonmostTcellsinautoimmunelesions
CD60a
CD60b
CD60c
CD61
CD62E
CD62L
CD62P
CD63
CD64
AkaFcgammaRI
HighaffinityreceptorbindstoFcregionofIgG
CD65
CD65s
CD66a
CD66b
Positivestaining(normal):granulocytes
Positivestaining(disease):chronicmyelogenousleukemia
CD66c
CD66d
CD66e
CD66f
CD67
CD68
CD69
CD70
CD71
CD72
CD73
CD74
CD75
CD75s
CDw76
Deletedat7thHLDAWorkshop;seenewCD75s
CD77
CDw78
Deletedat7thHLDAWorkshop
CD79a
CD79b
CD80
CD81
CD82
CD83
CD84
CD85
ILT/LIRfamily
InhibitoryMHCclassIreceptorpreventskillingbyNKandTcells
CD86
CD87
SubjecttonegativefeedbackregulationbyuPA,whichcleavesitintoaninactiveform
CD88
CD89
CD90
CD91
Positivestaining(normal):fibroblasts,dendriticcells,macrophages;liver,brain,lung
Microimages:psoriasis
CDw92
CD93
CD94
CD95
CD96
CD97
CD98
CD99
AkaPEN5
Positivestaining(normal):smallandlargebowelepithelia;lung,thyroidepithelia
Positivestaining(tumors):colorectalcarcinoma,pancreaticadenocarcinoma
AkaGlycophorinA
AkaGlycophorinB
AkaGlycophorinA/Bcrossreactiveantibodies
AkaGlycophorinC/D
AkaGlycophorinC
Regulatesmechanicalstabilityofredcells
MutationscauseGerbichandYusbloodgroupphenotypes
Noinformationavailable
AkaKellbloodgroupantigen
AkaLutheranbloodgroupantigen;B-CAM
AkaRhesus(Rh)bloodgroup,CcandEebloodgroupantigens
AssociateswithRh50,CD47andglycophorinBtoformtheRhantigen
AkaRhesus(Rh)bloodgroup,Dbloodgroupantigens
MajorantigenoftheRHsystem
AssociateswithRh50,CD47andglycophorinBtoformtheRhDgroup
CrossreactivetoRh30D/CEmonoclonalantibodies