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CD Markers CD100 to CD400
Last revised: 12 July 2009
Author: Nat Pernick, M.D., PathologyOutlines.com, Inc.
Copyright: (c) 2002-2009, PathologyOutlines.com, Inc.
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Note: no/minimal information is available on CDw145, CD182, CD185-194, CD196-199, CD211, CD214-216, CD218-220, CD237
Primary references
American Journal of Clinical Pathology (AJCP), August 1975 to August 2007
American Journal of Surgical Pathology (AJSP), March 1977 to August 2007
Archives of Pathology and Lab Medicine (Archives), January 1976 to July 2007
Biomed Center, 1 March 1997 to 8 August 2007
Human Pathology (Hum Path), March 1970 to August 2007
Modern Pathology (Mod Path), January 1988 to August 2007
Rosai, J: Ackerman’s Surgical Pathology (9th Ed); Mosby, 2004
Sternberg, S: Diagnostic Surgical Pathology (4th Ed); Lippincott Williams & Wilkins, 2004
University of Pittsburgh Medical Center Case Reports
CD Marker websites: http://ca.expasy.org/cgi-bin/lists?cdlist.txt, Protein Reviews On the Web, http://www.ebioscience.com/ebioscience/whatsnew/humancdchart.htm
Also called SEMA4D, semaphorin 4D
Integral membrane protein and ligand for CD72 and plexin-B1
Functions:
(a) regulates axonal growth cone guidance in the developing CNS through its receptor plexin-B1, which may be related to its expression in invading islands of transformed epithelial cells (but not normal and noninvasive dysplastic epithelium, Proc Natl Acad Sci USA 2006;103:9017)
(b) evokes angiogenic responses from endothelial cells (Blood 2005;105:4321)
(c) impairs monocyte migration
(d) after vascular injury, platelet associated CD100 binds to CD100 receptors on nearby platelets to promote thrombus formation (Proc Natl Acad Sci USA 2007;104:1621)
(e) increases CD45 induced T cell adhesion
(f) down regulates B cell expression of CD23
Expression may have prognostic value in soft tissue sarcoma (Cancer 2007;110:164)
Uses: no significant clinical use by pathologists
Positive staining (normal): most hematopoietic cells including platelets, increased expression after T cell activation
Negative staining: immature bone marrow cells
Micro images: head and neck squamous cell carcinoma
References: OMIM 601866, Wikipedia (semaphorins)
Also called immunoglobulin superfamily member 2 (IGSF2), V7
Inhibits T cell activation induced by CD3, by (a) inhibiting IL-2RA expression on activated T cells and IL2 secretion (J Immunol 1998;161:209), (b) inducing IL10 production (Eur J Immunol 2000;30:3132)
Uses: no significant clinical use by pathologists
Positive staining (normal): monocytes, granulocytes, dendritic cells, activated T lymphocytes in small intestine
Positive staining (disease): CD4+ CD56+ blastic tumor cells (J Invest Dermatol 2005;124:668), Langerhans cell histiocytosis (Histopathology 2000;36:229)
Micro images: CD4+ CD56+ blastic tumor cells
References: OMIM 604516, J Immunol 1998;161:2780
Also called ICAM-2
Binds the leukocyte integrins LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18)
Provides costimulatory signal in immune response; important in lymphocyte recirculation (J Immunol 2003;171:2588)
Endothelial ICAM-2 mediates angiogenesis (Blood 2005;106:1636)
Elevated serum levels in (a) hemorrhagic fever with renal syndrome (Viral Immunol 2006;19:565) and (b) idiopathic pulmonary fibrosis (Inflammation 2004;28:359)
Uses: no significant clinical use by pathologists
Positive staining (normal): resting lymphocytes, monocytes, platelets, vascular endothelial cells
Positive staining (disease): some lymphomas
Negative staining: neutrophils
References: OMIM 146630
Also called human mucosal lymphocyte antigen 1, integrin alpha E beta 7
CD103+ tumor infiltrating lymphocytes have a cytotoxic antitumor effect (J Exp Med 2007;204:559), may play a role in renal allograft rejection (Am J Transplant 2004;4:1026, J Exp Med 2002;196:873)
Uses: marker for hairy cell leukemia, intraepithelial lymphocytes (normal or tumor)
Positive staining (normal): intraepithelial T lymphocytes (90% in GI, tonsil-J Immunol 2005;175:4355, 30% in lung-Clin Exp Immunol 2007;149:162), lamina propria T lymphocytes in the intestine (50%), dendritic cells in gut (J Exp Med 2005;202:1051), rare peripheral blood lymphocytes
Positive staining (disease): hairy cell leukemia (usually, AJCP 2006;125:251), enteropathy-associated T cell lymphoma, splenic marginal zone lymphoma (some)
Flow cytometry images: hairy cell leukemia variant often expresses CD103 but not CD25 #1; #2 (fig C)
References: OMIM 604682
Also called integrin beta 4 chain
Tends to associate with alpha 6 subunit (CD49f)
Adhesion receptor (for laminins) in normal epithelia that plays a critical role in structure of hemidesmosomes; associated with intermediate filaments
May contribute to tumor progression (Cancer Metastasis Rev 2005;24:413) via VEGF stimulation (J Cell Biol 2002;158:165)
Overexpressed in pancreatic adenocarcinoma (J Histochem Cytochem 2005;53:799)
Mutations are associated with epidermolysis bullosa with pyloric atresia (Exp Dermatol 2004;13:61)
Uses: no significant clinical use by pathologists
Positive staining (normal): epithelium, thymocytes, Schwann cells
Positive staining (disease): carcinomas (some)
Micro images: normal pancreas and adenocarcinoma
References: OMIM 147557
Also called endoglin
Regulatory component of TGF-beta receptor complex; mediates cellular response to TGF-beta 1
Mutations cause Hereditary Hemorrhagic Telangiectasia type I (Am J Hum Genet 1997;61:68)
Required for hemangioblast and early hematopoietic development (Development 2007;134:3041)
Uses: specific and sensitive marker for tumor angiogenesis (better than CD31)
Poor prognostic factor - increased microvessel staining: acute lymphoblastic leukemia in children (Leuk Res 2007 Jun 15; [Epub ahead of print]), breast carcinoma (AJCP 2003;119:374, including node negative-Hum Path 2004;35:176), chronic idiopathic myelofibrosis (Mod Path 2004;17:1513), colorectal carcinoma (Mod Path 2004;17:197), endometrial carcinoma (Gynecol Oncol 2006;103:1007), esophageal adenocarcinoma (Hum Path 2006;37:861), gastric carcinoma (Hum Path 2006;37:861), hepatocellular carcinoma (BMC Cancer 2006;6:110), meningioma (Acta Neuropathol (Berl) 2007;114:147), ovarian carcinoma (Int J Gynecol Cancer 2006;16:1789), primary CNS lymphoma (J Neurooncol 2007;82:249), prostate adenocarcinoma (AJCP 2007;127:572), squamous cell carcinoma of head and neck (Virchows Arch 2006;448:768), including tongue (Laryngoscope 2006;116:1175)
Poor prognostic factor - other: serum endoglin is associated with intrauterine growth retardation during pregnancy (J Clin Endocrinol Metab 2007;92:2831), preeclampsia (N Engl J Med 2006;355:992, Nat Med 2006;12:642), diabetic retinopathy (J Cell Mol Med 2005;9:692)
Tissue endoglin is associated with progressive hepatic fibrosis in chronic HCV infection (J Viral Hepat 2006;13:625) and aortic atherosclerosis (J Atheroscler Thromb 2006;13:82)
Positive staining (normal): activated monocytes, erythroid precursors in marrow; syncytiotrophoblast, cytotrophoblast in first trimester (transient expression)
Positive staining (disease): endometriosis (Reprod Biol 2005;5:51), tumor microvessels (Rom J Morphol Embryol 2007;48:41)
Negative staining: normal endothelial cells (or weak)
Micro images: chronic idiopathic myelofibrosis (fig c, e, f); endometriosis (fig 3-5); liver-normal liver (fig 4); hepatocellular carcinoma #1; #2 and normal liver; lung-non small cell carcinoma (fig D)
References: J Transl Med 2004;2:18
Also called VCAM-1 (vascular cell adhesion molecule 1); alpha 4 beta 1 ligand
Interacts with beta 1 integrin VLA4
Adhesion molecular in activated endothelium; plays a role in migration of white blood cells (J Exp Med 2006;203:2763)
May mediate endothelial progenitor cell recruitment to rheumatoid arthritis synovium (Arthritis Rheum 2007;56:1817); associated with type II rheumatic disease (Cell Mol Biol (Noisy-le-grand) 2002;48 Online Pub:OL243)
Important in initiation of atherosclerosis (J Clin Invest 2001;107:1255)
Renal cell carcinoma may exploit VCAM-1 overexpression for immune system escape (Cancer Res 2007;67:6003); on the other hand, down regulation in breast cancer is associated with nodal metastases (Pathol Oncol Res 2002;8:125)
Increased expression: in placentas of women with pregnancy induced hypertension complicated by intrauterine growth retardation (Di Yi Jun Yi Da Xue Xue Bao 2002;22:1022)
Increased plasma levels: associated with: breast cancer [high stage] with circulating cancer cells (Neoplasma 2006;53:538), cancer (general)-early stage or preclinical (Eur J Cancer 2005;41:2355), dengue virus infection severity (J Med Virol 2004;72:445), diabetes with poor control (high HbA1c-Diabetes Care 2007;30:159 or arteriosclerosis obliterans-Clin Chim Acta 2007;377:198), endometriosis-advanced (J Soc Gynecol Investig 2002;9:98), sickle cell trait in athletes (J Appl Physiol 2007;102:169)
Uses: marker of endothelial damage (Endothelium 2006;13:335)
Positives staining (normal): activated endothelial cells, lymphocytes, monocytes, neural cells, hematopoietic cells
Positive staining (disease): renal cell carcinoma
Micro images: squamous cell carcinoma-well differentiated
References: OMIM 192225
Also called lysosome associated membrane protein 1 (LAMP-1)
Note: DC-LAMP is CD208
Functions:
(a) surface antigen transiently present on cell surface of CD8+ T cells after release of cytolytic granules (J Immunol Methods 2003;281:65)
(b) basophil activation antigen (Cell Res 2005;15:325)
(c) expression correlates with aggressiveness of melanocytic neoplasms (Melanoma Res 2006;16:235)
(d) critical to phagosomes acquiring microbicidal capabilities (Cell Microbiol 2007 May 15; [Epub ahead of print])
(e) ligand to E-selectin mediated cell adhesion
Uses: defective CD107a surface expression discriminates between genetic subtypes of familial hemophagocytic lymphohistiocytosis (Blood 2006;108:2316); used to measure degranulation in CD8+ T cells by flow cytometry (Nat Med 2003;9:1377) and NK cell activity / cytolytic capacity (J Immunol Methods 2004;294:15)
Positive staining (normal): primarily endosome-lysosome membranes, 1-2% on plasma membrane; degranulated platelets (Blood Coagul Fibrinolysis 2003;14:249-53), activated neutrophils, T cells, endothelium
Diagrams: structure
References: OMIM 153330
CD107b
Also called lysosome associated membrane protein 2 (LAMP-2)
X linked
Major constituent of lysosomal membranes (also LAMP-1)
Functions:
(a) mutations cause Danon disease, a lysosomal glycogen storage disease with cardiomyopathy in adult women and men before age 20 years (N Engl J Med 2005;352:362, Circulation 2005;112:1612), Wolff-Parkinson-White syndrome, myopathy, variable mental retardation and retinopathy (Arch Ophthalmol 2007;125:231); skeletal and cardiac muscle cells have intracytoplasmic vacuoles containing glycogen and autophagic material
(b) levels decrease with age (J Cell Sci 2007;120:782)
(c) binding of substrates to LAMP-2 is limiting step in chaperone-mediated autophagy, a selective mechanism for the degradation of soluble cytosolic proteins in lysosomes (EMBO J 2006;25:3921)
(d) may be involved in infection induced involution of thymus via autophagy (Acta Biol Hung 2006;57:315)
(e) facilitates MHC class II presentation of cytoplasmic antigens (Immunity 2005;22:571)
(f) basophil activation antigen (Cytometry A 2004;61:62)
Uses: help differentiate cardiomyopathy due to Danon disease (LAMP-2 negative) from other causes (LAMP-2+, Intern Med 2007;46:757)
Positive staining (normal): lysosome membranes of various tissues, platelets (Thromb Haemost 1996;75:623)
Negative staining: cardiac and skeletal muscle in Danon disease (Neuromuscul Disord 2003;13:708)
Diagrams: structure
Micro images: loss of LAMP-2 in hypertrophic cardiomyopathy patient #1 with Danon disease (fig A, B); #2 (fig A); #3 (loss of staining in muscle and heart); LAMP2+ cardiac myocytes in non Danon disease cardiomyopathy (fig 1g)
References: OMIM 309060
Also called semaphorin 7A (SEMA7A) or John-Milton-Hagen (JMH) human blood group antigen
A semaphorin (Wikipedia)
Receptors are plexin C1 and beta1 integrins
Functions:
(a) genetic variations may play a role in decreased bone mineral density and risk of vertebral fracture (J Hum Genet 2006;51:112)
(b) extremely potent monocyte activator; stimulates chemotaxis and cytokine production (Scand J Immunol 2002;56:270)
(c) stimulates axon growth and guidance during development (Nature 2003;424:398)
(d) negative regulator of T cell responses (Immunity 2006;24:591)
(e) expression is correlated with the establishment of dentin-pulp complex terminal innervation (Matrix Biol 2005;24:232)
Positive staining (normal): erythrocytes, activated lymphocytes, odontoblasts, monocytes, keratinocytes, fibroblasts
References: OMIM 607961
Also called Platelet activation factor
Glycosylphosphatidylinositol-anchored cell surface protein
Carries the biallelic platelet-specific Gov antigen system; alloantibodies to HPA-15 residing on CD109 are implicated in refractoriness to platelet transfusion, fetal/neonatal alloimmune thrombocytopenia and posttransfusion purpura (Blood 2002;99:1692)
Positive staining (normal): activation antigen for platelets and T cells; subset of hematopoietic stem and progenitor cells (Exp Hematol 1999;27:1282); myoepithelial cells (breast, prostate [basal cells] salivary and lacrimal glands, Pathol Int 2007;57:245); widely expressed in other tissues
Negative staining: invasive ductal carcinoma (breast), prostate adenocarcinoma
References: OMIM 608859
Also called thrombopoietin receptor (TPO-R), myeloproliferative leukemia virus oncogene (MPL)
Binding to thrombopoietin induces megakaryocyte proliferation and differentiation and prevents apoptosis
Mutations present in some patients with congenital amegakaryocytic thrombocytopenia, characterized by severe congenital thrombocytopenia with no megakaryocytes in the bone marrow (Hum Mutat 2006;27:296)
MPL mutations in myelofibrosis patients are associated with more severe anemia (Br J Haematol 2007;137:244)
Thrombopoietin receptor agonists may be useful for treating thrombocytopenia (Blood 2007;109:4739)
Uses: differentiate essential thrombocythemia (variable but weak/negative staining) from reactive thrombocytosis (positive staining, Blood 2002;99:4131)
Positive staining (normal): hematopoietic stem cells and progenitor cells (J Transl Med 2006;4:9), megakaryocytes and progenitors, platelets
Diagrams: protein and site of various mutations
References: OMIM 159530, EntrezGene
Aka poliovirus receptor related 1 (PRR1), nectin1
Widely expressed adhesion molecule that is a component of the adherens junction; receptor for herpes simplex viruses 1 and 2
Positive staining (normal): cells from myeloid, monocyte, megakaryocytes and erythroid lineage, epithelial cells, neurons, endothelium
Aka poliovirus receptor related 2 (PRR2)
Adhesion molecule that is a component of the adherens junction; receptor for herpes simplex virus
Positive staining (normal): cells from myeloid, monocyte, megakaryocytes lineage, epithelial cells, neurons, endothelium
Also called nectin-3, poliovirus receptor-related protein 3 precursor
Aka granulocyte colony-stimulating factor receptor, G-CSFR
Specific regulator of myeloid proliferation and differentiation
Mutations present in some patients with severe congenital neutropenia
Positive staining (normal): granulocytes (all), monocytes, platelets, endothelium, placenta, trophoblastic cells
Positive staining (tumors): cultured tumor cells
Negative staining: eosinophils, lymphocytes, erythrocytes
Aka c-fms, receptor for macrophage colony stimulating factor, CSF-1R
Localized on cytoplasmic membrane; mediates biologic activity of CSF-1
v-fms is a viral oncogene present in the feline McDonough sarcoma virus (has several substitute mutations)
Related to platelet derived growth factor receptor, c-kit, vascular endothelial growth factor receptor, fibroblast growth factor receptor, high affinity nerve growth factor (TrkA)
Deficiency causes reduced osteoclasts and macrophages, abnormal bone remodeling and osteopetrosis, abnormal breast development and decreased fertility
Positive staining (normal): macrophages and precursors, osteoclasts, placental trophoblast, breast tissue, microglia, neurons, astrocytes
Positive staining (tumors): 10% AML, some endometrial, ovarian and breast cancers, vascular smooth muscle cells in atheromas, choriocarcinoma cells
GM-CSF receptor alpha chain
Primary binding subunit of GM-CSF receptor
Positive staining (normal): monocytes, neutrophils, eosinophils, fibroblasts, endothelial cells, dendritic cells
Summary: proto-oncogene activated in GIST tumors
Aka c-kit, stem cell factor receptor
Gene at 4q11-21
Receptor for kit protein, a 145 kD tyrosine kinase growth factor receptor protein important for development and survival of mast cells, hematopoietic stem cells, melanocytes, germ cells, interstitial cells of Cajal
Has activating or gain of function mutations in most GIST tumors, often at exon 11, less often at exons 9 and 13, Hum Path 2002;33:484
Tyrosine kinase activity of c-kit in GIST and bcl-abl overexpression in CML are inhibited by imatinib mesylate (Gleevec, STI571), a tyrosine kinase inhibitor used to treat these diseases, Hum Path 2002;33:466
Uses: confirming diagnosis of GIST (but see other CD117+ tumors below), possibly confirm chronic intestinal pseudo-obstruction, AJSP 2003;27:228
Interpretation: should be strong and diffuse cytoplasmic staining, like the positive control
Positive staining (normal): interstitial cells of Cajal, hematopoietic progenitor cells, melanocytes, embryonic/fetal brain, endothelium, gonads, mast cells, breast epithelium, germ cells
Positive staining (tumors): AML, angiomyolipoma (AJSP 2002;26:493), angiosarcomas (50%), clear cell sarcoma, CML, epithelioid sarcoma, Ewing sarcoma, gastrointestinal autonomic tumors, gastrointestinal stromal tumors (GIST), granulocytic sarcoma, Hodgkin’s lymphoma (some Reed-Sternberg cells), intraabdominal fibromatosis (depends on antibody used, AJSP 2001;25:549), mast cell disease (also positive for tryptase, CD43, CD68); melanoma, mesenteric fibromatosis (variable, AJSP 2002;26:1296), metanephric adenosarcoma (AJSP 2001;25:1451), omental mesenchymal tumor, osteosarcoma, rhabdomyosarcoma, sclerosing mesenteritis (variable), seminomas /dysgerminomas, small cell lung cancer (Hum Path 2002;33:1182), synovial sarcoma (~10%, usually cytoplasmic staining), adenoid cystic carcinoma of salivary gland (strong staining)
Negative staining: alveolar soft part sarcomas, desmoplastic small round cell tumors, glomus tumors, leiomyomas (retroperitoneal, colorectal), leiomyosarcomas, myxomas (cardiac), schwannomas (colorectal), smooth muscle tumors of uncertain malignant potential, solitary fibrous tumors
Micro images: GIST vs. solitary fibrous tumor; malignant stromal tumor of gallbladder (figure 4); GIST (figures G, H); interstitial cells of Cajal in patient with multiple GIST tumors
References: Archives 2002;126:1189, AJSP 2002;26:486
Reserved for interferon alpha / gamma receptor
Interferon gamma receptor
Positive staining (normal): macrophages, B cells
Aka TNFR1, receptor for tumor necrosis factor alpha and beta, type I
Receptor binding to ligand causes apoptosis
CD120b
Aka receptor for tumor necrosis factor (TNF) alpha and beta, type II
Aka Interleukin 1 receptor (IL-1R) type I, IL1-alpha
Interleukin-1, an inflammatory mediator, consists of 2 separate but related proteins, IL1-alpha and IL1-beta
Positive staining (normal): T cells, thymocytes, fibroblasts, endothelial cells
CDw121b
Aka Interleukin 1 receptor (IL-1 R) type II, IL1-beta
May inhibit IL1 activity by acting as a decoy target for IL1
Positive staining (normal): B cells, macrophages
Aka Interleukin 2 receptor beta chain (IL-2R beta)
Critical component of IL-2 and IL-15-mediated signaling
Positive staining (normal): NK cells, B cells, T cells, monocytes
Aka Interleukin 3 receptor alpha subunit
Associates with the GM-CSF receptor (GMR beta)
Positive staining (normal): plasmacytoid monocytes (bright with flow cytometry, AJSP 2002;26:852)
Aka Interleukin 4 receptor
Receptor subunit for Interleukin-4 and 13
Positive staining (normal): mature B cells, T cells; hematopoietic precursors; fibroblasts, endothelial cells
Aka Interleukin 5 receptor alpha subunit
Therapeutic target of eosinophilic inflammation involved in bronchial asthma
Positive staining (normal): eosinophils, activated B cells, basophils
Aka Interleukin 6 receptor
Continuous expression of IL-6 and CD130, ligands for CD126, causes hypergammaglobulinemia, glomeruloproliferative nephritis and lymphoid infiltration in some organs
Dysregulated stimulation may cause myeloma and plasmacytoma
Positive staining (normal): T cells, monocytes, activated B cells, hepatocytes
Aka Interleukin 7 receptor
Positive staining (normal): B cell precursors, most T cells, monocytes
See CD181
CDw128b
Aka Interleukin 8 receptor beta subunit, CXCR2
Chemokine receptor, powerful neutrophil chemotactic factor, particularly to sites of inflammation
Binds multiple CXC chemokines including IL-8
Positive staining (normal): mature granulocytes, projection neurons, neuroendocrine cells (various)
Positive staining (tumors): carcinoids, atypical carcinoids, metastatic carcinoids, pituitary adenomas, pheochromocytomas, medullary carcinomas
Negative staining: small cell carcinoma of lung/cervix, large cell lung neuroendocrine carcinoma, Merkel cell carcinoma, neuroblastoma, melanoma
Reserved for Interleukin 9 receptor
Aka gp 130
Required for transducing biological activities of interleukin-6, interleukin-11, leukemia inhibitory factor, ciliary neurotrophic factor, oncostatin M, and cardiotrophin-1
In human, IL-6 and oncostatin M dependent activation of gp130 are involved in multiple myeloma
Positive staining (normal): almost all cell types (low levels)
Aka common beta subunit
Does not bind any cytokine by itself, but is a component of the high affinity IL-3, GM-CSF and IL-5 receptors
Defective CDw131 is associated with protein alveolar proteinosis
Positive staining (normal): myeloid (early and mature), early B cells
Aka common cytokine receptor gamma chain - receptor for IL-2, IL-4, IL-7, IL-9 and IL-15
Mutation in humans causes X-linked severe combined immunodeficiency (no T cells, no NK cells)
CD132 is a target molecule for gene therapy for X-SCID
Positive staining (normal): T cells, B cells, NK cells, monocytes/macrophages, neutrophils
Aka prominin-like 1, AC 133
Alternative to CD34 in selecting hematopoietic stem and progenitor cells for transplantation studies
Localized to microvilli and other plasma membrane protrusions
Positive staining (normal): CD34 bright hematopoietic stem and progenitor cells, neural and endothelial stem cells, other primitive cells such as retina, villous and extravillous cytotrophoblast, syncytiotrophoblast
Positive staining (tumors): retinoblastoma, hemangioblasts, developing epithelium
Negative staining: adult epithelial tissue, villous stroma
Aka tax-transcriptionally activated glycoprotein 1 receptor, OX40 antigen, lymphoid activation antigen
Aka FMS-like tyrosine kinase 3, flt3
Growth factor receptor for early hematopoietic progenitors
Positive staining (normal): multipotential, myelomonocytic, and primitive B cell progenitors
Positive staining (tumors): most AML, ALL and CML
Aka macrophage stimulating protein receptor, msp receptor
May regulate ciliary beat frequency in epithelial cells
Positive staining (normal): skin, kidney, lung, liver, intestine, and colon
Costimulator of T cell proliferation
Positive staining (normal): T cells, especially CD45RA and CD45R0; also B cells, monocytes, epithelial cells
Aka heparan sulfate proteoglycan, syndecan-1
Mediates cell adhesion, growth factors; associated with late stage of B cell differentiation
Integral membrane protein is a receptor for extracellular matrix
Loss of CD138 expression is associated with tumor aggressiveness in squamous cell carcinoma (SCC) of head and neck and larynx; levels also reduced in invasive SCC but not in SCC-in situ
Interpretation: membranous staining
Positive staining (normal): B cell precursors, plasma cells, stratified squamous epithelium
Positive staining (tumors): keratoacanthoma, myeloma, plasmablastic lymphoma (strong), primary effusion lymphoma, pyothorax associated lymphoma
Negative staining: mature B cells, other lymphomas (even plasmacytoid lymphomas)
Micro images: keratoacanthoma #1 (figure B); #2 (figure B); invasive squamous cell carcinoma
References: Mod Path 2002;15:45; AJSP 2002;26:1363
Positive staining (normal): B cells, monocytes, granulocytes, erythrocytes (weak), dendritic cells, glomeruli
Negative staining: T cells
Aka alpha platelet derived growth factor receptor
CD140b
Aka beta platelet derived growth factor receptor
Aka thrombomodulin
75kD transmembrane glycoprotein and cofactor for the thrombin-mediated activation of protein C
Marker of mesotheliomas, endothelial cells and coagulation factor
Important fibrinolytic inhibitor, as it decreases the activation of plasminogen to plasmin
Critical for activation of protein C and initiation of the protein C anticoagulant pathway
Plasma CD141 levels are associated with endothelial damage
Interpretation: membranous staining pattern, often focal (cytoplasmic staining may be artifactual)
Uses:
Mesothelioma vs. lung adenocarcinoma: 64% sensitive, 95% specific for mesotheliomas, but must exclude vasculature; often membranous staining of periphery with isolated papilla; negative staining in sarcomatoid mesotheliomas; considered to have a “secondary” role as other markers are better, Hum Path 2002;33:953
Urothelial carcinomas (positive) vs. renal cell, prostate, endometrial or colonic carcinomas, AJSP 2001;25:1380
Squamous cell carcinomas (positive), AJCP 1998;110:385, AJSP 2003;27:150
Positive staining (normal): endothelial cells, megakaryocytes, keratinocytes, mesothelial cells, monocytes, neutrophils, platelets, smooth muscle cells, syncytiotrophoblasts, synovial lining cells, urothelium
Positive staining (tumors): mesothelioma (epithelioid), squamous cell carcinomas, trophoblastic tumors, urothelial carcinomas, vascular tumors (including angiosarcoma), synovial sarcoma (diffusely positive in 10%, AJSP 2001;25:610)
Negative staining: adenocarcinoma of colon, endometrium, kidney, lung (usually), prostate; sarcomatoid mesothelioma,
Aka coagulation Factor III, thromboplastin, tissue factor
Major initiator of clotting in normal hemostasis and many thrombotic diseases, via complex with factor VIIa
Also binds zymogen factor VII, the inactive precursor form; once bound, a variety of serine proteases rapidly activate factor VII to VIIa via limited proteolysis
Normally absent from all cells in direct contact with plasma
Positive staining (normal): epidermal keratinocytes, glomerular epithelial cells and various other epithelia, adventitial cells of blood vessels, astrocytes, myocardium, Schwann cells, stromal cells of liver, pancreas, spleen and thyroid
Aka angiotensin-converting enzyme, ACE, peptidyl dipeptidase A
Involved in metabolism of angiotensin II and bradykinin; also cleaves substance P and LH-RH
Patients with high activity have DD genotype, associated with MI, strokes, diabetic nephropathy
Necessary for spermatozoa to bind to egg and associated with better penetration of egg
Positive staining (normal): endothelial cells of small/medium arteries, lung capillary endothelium, proximal renal tubule brush borders, basal ganglia neuropil, granulosa cells, Leydig cells, variable on other cells
Endothelial-specific cadherin localized at intercellular junctions
Aka vascular endothelial-cadherin precursor, VE-cadherin, cadherin 5
Cadherins are cell adhesion proteins that preferentially interact with themselves in a homophilic manner in connecting cells, thus contributing to the sorting of heterogeneous cell types
Positive staining (normal): endothelial cells, brain
May be expressed by endothelial cells
No other information available
Aka melanoma cell adhesion molecule (MEL-CAM), cell surface glycoprotein MUC18
May be a neural crest cell adhesion molecule during embryogenesis
Associated with tumor progression and the development of metastasis in human malignant melanoma
Sensitive but nonspecific marker of desmoplastic/spindle cell melanoma; use if suggestive histology, S100 positive, melanoma markers otherwise negative, AJSP 2001;25:58
Interpretation: expression is membranous
Positive staining (normal): vascular smooth muscle, endothelium, intermediate trophoblast in exaggerated placental sites and placental site trophoblastic tumors (Hum Path 1999;30:687), subpopulation of T cells, endothelium, smooth muscle, Schwann cells
Positive staining (tumors): clear cell sarcoma (90%), leiomyosarcomas (almost all), melanoma (desmoplastic-84%, epithelioid melanomas-100%, advanced primary tumors and metastatic tumors), melanotic schwannoma (100%), MPNST (27%), neurofibroma (40%), prostatic adenocarcinoma and high grade PIN, squamous cell carcinomas (some), vascular sarcomas (almost all)
Negative staining: normal melanocytes, melanocytic nevi, cellular blue nevus, thin primary melanomas, placental site nodules (or focal), epithelioid trophoblastic tumors (or focal), cytotrophoblast, atypical fibroxanthoma
Reference: AJSP 2001;25:58
Aka neurothelin, extracellular matrix metalloproteinase inducer
Positive staining (normal): all leukocytes, red blood cells, platelets and endothelial cells
Aka HPTP-eta
May be involved in contact inhibition of cell growth
Positive staining (normal): granulocytes, monocytes, memory T cells, dendritic cells, platelets, fibroblasts, neurons, Kupffer cells
Deleted (now designated CD47R) at the 7th HLDA Workshop
Reference: Tissue Antigens 2000;56:258
Aka signal lymphocyte activation molecule (SLAM)
Costimulatory molecule on B lymphocytes and dendritic cells
Positive staining (normal): thymocytes, CD45RO positive subpopulation of T cells, B cells, dendritic cells, endothelium
May modify integrin function or signaling
Positive staining (normal): endothelium, platelets, megakaryocytes, epithelium
Aka cytotoxic T lymphocyte-associated protein-4, CTLA4
Negative regulator of T cell activation
CTLA4 restriction fragment length polymorphisms are linked to various autoimmune disorders
Shares sequence homology with CD28; also shares ligands CD80 and CD86 with CD28
Positive staining (normal): activated but not resting T cells, activated B cells
References: 123890
Aka CD30 ligand
Enhances CD3-activated T lymphocyte proliferation
Aka CD40 ligand, CD40L, TNF-related activation protein (TRAP)
Regulates B cell function by engaging CD40
Defective gene prevents immunoglobulin class switch and is associated with hyper IgM syndrome, autoimmune hematologic disorders, disorganized nodal follicular architecture and PAS-positive plasmacytoid cells containing IgM, lymph nodes without germinal centers, shortened lifespan, often with gastrointestinal cancers (cholangiocarcinoma, hepatocellular carcinoma, and adenocarcinoma) and Cryptosporidium parvum infection
Positive staining (normal): T cells
Aka polio virus receptor
Involved in intercellular adhesion
Positive staining (normal): embryonic structures giving rise to spinal cord anterior horn motor neurons
Aka ADAM8
May play a role in muscle differentiation
Possible role in neutrophilic extravasation
Positive staining (normal): neutrophils, monocytes
CD156b
Aka Tumor necrosis factor Alpha Converting Enzyme (TACE), ADAM17
Adhesion structure; releases soluble forms of tumor necrosis factor and transforming growth factor-alpha from cells
Positive staining (normal): all cells examined, with pro-domain removed
Aka Bone marrow STromal cell antigen 1 (BST1)
Facilitates pre-B-cell growth
33% homology to CD38
Overexpression may cause polyclonal B-cell abnormalities in rheumatoid arthritis
Positive staining (normal): granulocytes, monocytes, B cell progenitors, T cell subpopulations
Member of KIR (killer cell immunoglobulin like receptor) family, also called killer cell inhibitory receptors
Binding by HLA class I molecules causes inhibition of NK or T cell cytotoxic activity
Melanoma specific cytotoxic T lymphocytes may express KIR and regulate their ability to kill these tumors
Positive staining (normal): Natural killer cells (NK cells), some T cells
CD158a
Aka KIR2DL1/p58.1
Regulates NK cell mediated cytolytic activity
Includes two different molecules with inhibitory and activation effects, presumably encoded by different genes of the same family
Positive staining (normal): NK cell subset
CD158b
CD158b1 aka KIR2DL2/p58.2
CD158b2 aka KIR2DL3/p58.3
Regulates NK cell mediated cytolytic activity
Includes two different molecules with inhibitory and activation effects, presumably encoded by different genes of the same family
Positive staining (normal): NK cell subset, rare T cells
CD158c-KIR2DS6/KIRX
CD158d-KIR2DL4
CD158e1-KIR3DL1/p70
CD158e2-KIR3DS1/p70
CD158f-KIR2DL5
CD158g-KIR2DS5
CD158h-KIR2DS1/p50.1
CD158i-KIR2DS4/p50.3
CD158j-KIR2DS2/p50.2
CD158k-KIR3DL2/p140
CD158z-KIR3DL7/KIRC1
Aka NKG2A, killer cell lectin-like receptor subfamily C member 1
Mediates signaling in the killing process by NK cells
Positive staining (normal): NK cells
Aka BY55
Expression tightly associated with peripheral blood NK cells and CD8+ T lymphocytes with cytolytic effector activity
Positive staining (normal): circulating NK (CD56 dim, CD116+) and T cells, spleen, small intestinal intraepithelial lymphocytes
Aka killer cell lectin-like receptor subfamily B, member 1
May mediate NK cell function
Positive staining (normal): NK cells, subset of CD4+ and CD8+ T cells, memory T cells, thymocytes (some)
Aka P-Selectin Glycoprotein Ligand 1, PSGL-1
Important in adhesive interactions between circulating leukocytes and platelets and endothelial cells
Mediates rolling on activated endothelium or activated platelets (which express P selectin / CD62P) and other leukocytes at inflammatory sites
Site of binding of human granulocyte ehrlichiosis bacteria
Positive staining (normal): myeloid cells, stimulated T cells
CD162R
Aka PEN5
Positive staining (normal): NK cells
Hemoglobin/haptoglobin scavenger receptor
Soluble form attenuates immune response
Positive staining (normal): monocytes/macrophages
Positive staining (disease): histiocytic sarcoma (Diagn Pathol 2007;2:7)
Micro images courtesy of Drs. Charles J. Sailey, Borislav A. Alexiev and John C. Papadimitriou, Maryland (USA): histiocytic sarcoma
Aka MUC-24, sialomucin
Mucin-like cell surface glycoprotein that facilitates adhesion of CD34+ cells; regulates hematopoietic cell proliferation
Positive staining (normal): small and large bowel epithelia; lung, thyroid epithelia
Positive staining (tumors): colorectal carcinoma, pancreatic adenocarcinoma
Involved in adhesion between thymocytes and thymic epithelial cells
Positive staining (normal): immature thymocytes, monocytes, platelets, CNS neurons, islet cells, Bowman’s capsule of kidney
Positive staining (tumors): many T-acute lymphoblastic leukemias (ALL)
Aka Activated Leukocyte Cell Adhesion Molecule (ALCAM)
Adhesion molecule, binds to CD6
Involved in neuronal neurite extension, embryonic hemopoiesis, embryonic angiogenesis
Positive staining (normal): neurons, activated T cells, activated monocytes, epithelium, fibroblasts
Aka Discoidin Domain Receptor 1, DDR1
Has homologous region to the Dicytostelium discoideum protein discoidin I in extracellular domain
Tyrosine kinase receptor, may be important in cytoskeletal organization and the ability to align with other cells during aggregation
Receptor tyrosine kinases help cells communicate with their microenvironment and regulate cell growth, differentiation and metabolism.
Activated by collagen types I-V, VIII
May have a role in tumor invasion and metastasis
Positive staining (normal): epithelial cells (breast, kidney, lung, GI, brain)
Positive staining (tumors): carcinomas (various)
Aka Receptor for Hyaluronic Acid-Mediated Motility (RHAMM)
Binding to hyaluron stimulates ciliary beating
Also has role in cell signaling, migration and adhesion
Positive staining (normal): bronchial epithelium, CNS neurons
Aka sialoadhesin
Macrophage-restricted cellular interaction molecule that binds sialylated ligands
Highly expressed on macrophages in chronically inflamed tissues, such as rheumatoid synovium and atherosclerotic plaques
Positive staining (normal): macrophages (all sites but microglia)
Negative staining: microglia
Aka Sialic acid binding IG-like LECtin 5 (SIGLEC5)
May function in cell-cell interaction
Positive staining (normal): neutrophils
Aka L1
Adhesion molecule required for normal neurohistogenesis
Mutations cause CRASH (Corpus callosum hypoplasia/agenesis, Retardation, Aphasia, Spastic paraplegia/shuffling gait and Hydrocephalus due to stenosis of aqueduct of Sylvius), an X linked neurologic disorder
May mediate kidney branching morphogenesis, maintenance of lymph node architecture during immune response, co-stimulation of T-cell activation in vitro
Positive staining (normal): post-mitotic neurons, glia, epithelial cells (some), lymphoid cells (some), myeloid (some), monocytes
Aka SIRP alpha
Adhesion structure
Aka blood group H2
Marker of early hematopoiesis
Positive staining (normal): CD34+ hematopoietic progenitor cells
Negative staining: mature lymphocytes
Aka Lewis Y antigen
Marker of early hematopoiesis
Positive staining (normal): CD34+ hematopoietic progenitor cells
Negative staining: mature lymphocytes
Aka Tn
Simple mucin-type carbohydrate antigen produced in the initial steps of mucin biosynthetic pathway, due to aberrant or incomplete glycosylation of mucins
CD175s
Aka Sialyl Tn (STN)
Carbohydrate associated with apomucins MUC1, MUC2; produced in the initial steps of mucin biosynthetic pathway
Presence associated with aggressive tumors
High pre-operative serum levels predict liver metastasis and poor prognosis after resection for gastric cancer
Definitive Phase III trial of STN vaccine in metastatic breast cancer patients began 2001
Positive staining (tumors): carcinomas
Aka Thomsen-Friedenreich (TF) oncofetal blood group antigen, galactose beta 1-3 N-acetylgalactosamine alpha
Occurs in colon cancer and colitis
Aka NB1 glycoprotein
Major immunogenic molecule of neutrophil membrane
Positive staining (normal): myeloid cells
Aka CD95 ligand, Fas ligand (FasL)
Important role in T cell mediated cytotoxicity; induces apoptosis in Fas-expressing target cells
Cells in immune privileged sites (testis, anterior chamber of eye, placenta) constitutively express FasL, which induces apoptosis in Fas-expressing infiltrating T cells, minimizing inflammatory responses that might damage important physiologic functions at these sites
May influence interaction of tumor cells with host immune system; theory is that FasL+ tumor cells induce apoptosis in infiltrating Fas+ mononuclear cells
Fas-FasL binding triggers apoptosis in lymphocytes
Mutations may be related to some cases of Systemic Lupus Erythematosis (SLE)
Processed by metalloproteases which cause shedding of extracellular portion into blood (sFas L)
Positive staining (normal): activated and cytotoxic T cells, testis, anterior chamber of eye, placenta; also Sertoli cells, neurons, thyroid epithelial cells
Positive staining (tumors): Reed-Sternberg cells of Hodgkin’s lymphoma (nodular sclerosis and mixed cellularity, AJSP 2001;25:388)
Aka VpreB1
Associates non-covalently with CD179b to form surrogate light chain as component of preB cell receptor, which plays a critical role in early B cell differentiation
Positive staining (normal): preB cells
CD179b
Aka lambda-5
Associates non-covalently with CD179a to form surrogate light chain as component of preB cell receptor, which plays a critical role in early B cell differentiation
Mutations impair B cell development and cause agammaglobulinemia
Positive staining (normal): preB cells
Aka RP105
Regulates B cell recognition of lipopolysaccharide, a membrane constituent of gram-negative bacteria
Positive staining (normal): mantle zone and marginal zone B cells (strong), other B cells (weak/negative); peripheral blood monocytes, dendritic cells
Also called CXCR1, IL8Ralpha; previously called CDw128A
Chemokine receptor, powerful neutrophil chemotactic factor
Positive staining (normal): neutrophils, basophils, T cell subset, monocytes, keratinocytes
Positive staining (disease): T cells in allergic rhinitis (J Immunol 2004;172:268)
No information available
Aka CXCR3
Receptor for some chemokines; binding of chemokines to CD183 induces integrin activation, cytoskeletal changes and chemotactic migration in inflammation-associated effector T cells
CD183+ T cells detected in inflamed tissues of patients with juvenile rheumatoid arthritis, multiple sclerosis, sarcoidosis, hepatitis C
Positive staining (normal): T cells in inflamed tissue, eosinophils, plasmacytoid dendritic cells, hematopoietic progenitors
Negative staining: naïve T cells in peripheral blood
Aka CXCR4, Stromal cell Derived Factor 1 (SDF1)
Receptor for the CXC chemokine SDF-1
Also major HIV/SIV co-receptor (with CCR5/CD195)
Involved in B cell development, myelopoiesis, cardiac ventricular septum formation, blood vessel formation in GI tract, cerebellar granular cell development
Positive staining (normal): all mature blood cells, blood progenitor cells, endothelial and epithelial cells, astrocytes, neurons
No information available
No information available
No information available
No information available
No information available
No information available
No information available
No information available
No information available
No information available
Aka CCR5
Macrophage surface receptor and attachment site for HIV and SIV, with CXCR4 (CD184); works with CD4
Receptor for CD8 chemokines RANTES, MIP 1-alpha and MIP 1-beta.
No information available
Aka CCR7
No information available
No information available
Aka OX2
An immunoadhesin that may deliver immunosuppressive signals and regulate autoimmune disorders
Inhibitory for macrophage lineage cells
Positive staining (normal): follicular dendritic cells, thymocytes, B cells, T cells, neurons, kidney glomeruli, syncytiotrophoblast, endothelial cells
Binds protein C in a calcium-dependent manner
Aka Endothelial Protein C Receptor (EPC R), protein C receptor
Protein C is a vitamin K dependent enzyme with major role in coagulation of blood; activated when thrombin binds to thrombomodulin on endothelium.
Mutations in CD201 and thrombomodulin associated with late fetal loss; similar mutation associated with venous thromboembolism and myocardial infarction
Positive staining (normal): endothelial cells (not in liver and kidney)
Aka Tie2 (Tyrosine kinase with Ig-like loops and Epidermal growth factor homology domains), aka Tek
Receptor tyrosine kinase at #9p21, binds to angiopoietin-1
May be earliest mammalian endothelial cell lineage marker
Involved in vein morphogenesis and communication between endothelial and smooth muscle cells for remodeling and repair of blood vessels
Defects associated with inherited venous malformations
Positive staining (normal): endothelial cells, hematopoietic cells
Aka E-NPP3/PDNP3
Enzyme that catalyzes hydrolysis of oligonucleotides, nucleoside phosphates, and NAD
Positive staining (normal): prostate, uterus, basophils, mast cells, gliomas, myeloid cells
Aka macrophage scavenger receptor 1
Plays a role in endocytosis of macromolecules
Positive staining (normal): myeloid cells
Aka DEC205
Possible antigen-uptake receptor with a role in initiating immune response
Positive staining (normal): dendritic cells
Aka macrophage mannose receptor
Acts in phagocytosis and pinocytosis of mannose-containing solutes
Positive staining (normal): dendritic cells
Aka langerin (Langerhans cell specific c-type lectin)
Functions as endocytic receptor
Localized to Birbeck granules
Mannose binding to this protein may cause antigen internalization into Birbeck granules and access to a nonclassical antigen-processing pathway
Positive staining (normal): Langerhans cells (immature dendritic cells of epidermis and mucosa)
Dendritic cell LAMP (DC-Lamp)
Indicates dendritic cell maturation
Positive staining (normal): dendritic cells
Aka DC-Sign
Binds to HIV1 gp120
Mediates transient adhesion of dendritic cells with T cells
Positive staining (normal): dendritic cells
Aka IL-10 receptor
Interleukin-10 (124092) produced by B cells, T helper cells, and monocyte/macrophages, exhibits diverse activities on different cell lines
IL10 inhibits macrophage activation by interferon-gamma
Positive staining (normal): monocytes, B and T cells, large granular lymphocytes, spleen, thymus, placenta, lung, liver
No information available
Aka IL-12 receptor
Interleukin-12 promotes cell-mediated immunity to intracellular pathogens by inducing type 1 helper T cell responses and interferon-gamma production.
Lack of IL12 associated with severe, idiopathic mycobacterial and Salmonella infections, mature granulomas
Positive staining (normal): T cells, NK cells
Aka IL-13 receptor, alpha 1
Binds IL-13 with low affinity
With IL-4r-alpha, can form a functional receptor for IL-13
Positive staining (normal): ubiquitous, B-cells, T-cells and endothelial cells, highest levels in heart, liver, skeletal muscle and ovary
CD213a2
Aka IL-13 receptor, alpha 2
Inhibits binding of interleukin-13 to the IL13 cell surface receptor
Positive staining (normal): placenta
No information available
No information available
No information available
Aka IL 17 receptor
Cytokine that is induced in activated CD4+ T cells
IL17 induces stromal cells to produce proinflammatory and hematopoietic cytokines; enhances expression in fibroblasts of ICAM-1
No information available
No information available
Aka insulin receptor
Aka insulin-like growth factor 1 receptor
Mediates insulin stimulated DNA synthesis and IGF1 stimulated cell proliferation and differentiation
Often overexpressed in malignant tissue, where it functions as an anti-apoptotic agent by enhancing cell survival
Aka insulin-like growth factor 2 receptor, mannose 6 phosphate receptor
Also a receptor for lysosomal hydrolases (i.e. assists in sorting lysosomal enzymes from Golgi apparatus or extracellular space to lysosomes)
Aka Lymphocyte-Activation Gene 3 (LAG-3)
Homologous to CD4
Associates with MHC class II molecules on monocytes/dendritic cells, which are subsequently activated
May help activated CD4+ and CD8+ T cells to fully activate monocytes and dendritic cells, leading to optimized MHC class I and class II T cell responses
Positive staining (normal): activated T cells, activated NK cells
Aka gamma-glutamyltransferase
Gene at 22q11.1-q11.2
Catalyzes the transfer of the glutamyl moiety of glutathione to a variety of amino acids and dipeptide acceptors, which maintains a homeostatic balance regarding oxidative stress.
Aka Leu13, interferon-inducible transmembrane protein 1
Involved in relaying antiproliferative and homotypic adhesion signals
Aka DNAM-1, Platelet and T cell Activation antigen 1 (PTA1)
Mediates adhesion to an unknown ligand
T cell expression increased in some patients with autoimmune disease and viral infection
Positive staining (normal): NK cells, platelets, monocytes, subset of B and T cells
Negative staining: granulocytes, erythrocytes
Aka EMA, MUC1, episialin
Large cell surface mucin glycoprotein expressed by most glandular and ductal epithelial cells and some hematopoietic cells
Highly expressed by most adenocarcinomas, associated with poor prognosis, Hum Path 1995;26:432
Shed into the bloodstream of adenocarcinoma patients, used in commercial serum tumor marker assays (CA15-3)
Expressed by nearly all cases of Paget’s disease, can use to screen/confirm presence of Paget’s cells in epidermis, AJSP 2001;25:1469
Associated with invasion in pancreatic tumors, AJSP 2002;26:466
Positive staining (normal): apical surface of almost all glandular and ductal epithelial cells including breast and pancreas, activated T cells, monocytes, some B cells, follicular dendritic cells, perineurial cells
Positive staining (tumors): adenocarcinoma (most), anaplastic large cell lymphoma, epithelioid sarcoma, meningioma, mesothelioma (some), myeloma, Paget’s disease, plasmacytoma
Negative staining: hepatocellular and adrenal carcinoma, germ cell tumor
Micro images: urothelial carcinoma-high grade
References: J Leukoc Biol 2002;72:692
Aka melanotransferrin
Cell-surface glycoprotein found on melanoma cells, with sequence similarity and iron-binding properties of transferrin superfamily
Aka Lymphocyte antigen 9
May be involved in adhesion between T cells and accessory cells
Aka prion protein (“PRotein INfectious agent”)
Mutations associated with Gerstmann-Straussler disease, Creutzfeldt-Jakob disease (CJD), familial fatal insomnia, which are neurodegenerative conditions transmissible by inoculation or inherited as autosomal dominant disorders
Aberrant isoforms can act as an infectious agent in these disorders as well as in kuru and in scrapie in sheep
Replication (infectivity) occurs as abnormal protein with conformational change recruits cellular prion and converts it into infective form with same conformational change
Positive staining (normal): neurons (nonpathogenic isoform)
Reference: 176640
Aka T cell Acute Lymphoblastic Leukemia Antigen-1 (TALLA-1), TM4SF2, A15
Involved in X-linked mental retardation, Nat Genet 2000;24:167
Positive staining (normal): brain neurons
Positive staining (tumors): T cell acute lymphoblastic leukemia, neuroblastoma cells
Negative staining: B cells, monocytes
CD232
Aka Virus Encoded Semaphoring Protein Receptor (VESP R)
May function as an immune modulator during virus infection.
Aka band 3
Erythrocyte membrane protein that functions as an anion (chloride/bicarbonate) exchanger and attachment site for cytoskeleton (where spectrin/actin bind to membrane lipid bilayer)
Truncated form of CD233 is expressed in kidney and involved in acid secretion
Mutations cause hereditary spherocytosis or distal renal tubular acidosis (due to defective acid secretion)
Other mutations cause novel blood group antigens which form the Diego blood group system
Southeast Asian ovalocytosis is due to heterozygous deletions, common where Plasmodium falciparum malaria is endemic, associated with abnormally rigid, stomatocytic erythrocytes, asymptomatic; children are protected against cerebral malaria
Positive staining (normal): erythrocyte plasma membrane (strong), basolateral membrane of a-intercalated cells of the distal tubules and collecting ducts of the kidney
Negative staining: all other cells
Aka Duffy blood group antigen (Fy glycoprotein); erythrocyte chemokine receptor, Duffy Antigen Receptor for Chemokines (DARC)
RBC receptor for Plasmodium vivax, a malarial parasite
Negativity associated with sickle cell trait, due to common protection against malaria provided by both traits African-Americans often Duffy negative and resistant to P. vivax malaria
Positive staining (normal): endothelial cells of post-capillary venules, Purkinje cells of cerebellum
Aka Glycophorin A
Glycophorins A and B are major sialoglycoproteins of the human erythrocyte membrane
Contains antigenic determinants for the MN blood group
Positive staining (normal): erythroid cells
CD235b
Aka Glycophorin B
Glycophorins A and B are major sialoglycoproteins of the human erythrocyte membrane
Contains antigenic determinants for the MN blood group
Positive staining (normal): erythroid cells
CD235ab
Aka Glycophorin A/B crossreactive antibodies
Positive staining (normal): erythroid cells
Aka Glycophorin C/D
Positive staining (normal): erythroid cells
CD236 R
Aka Glycophorin CRegulates mechanical stability of red cells
Mutations cause Gerbich and Yus blood group phenotypes
Positive staining (normal): erythroid cells
No information available
Aka Kell blood group antigen
Positive staining (normal): erythroid cells
Aka Lutheran blood group antigen; B-CAM
May mediate cell-cell, cell-matrix adhesion, signal transduction
Positive staining (normal): erythroid cells
Also called RH 30 CE, Rh blood group Cc and Ee blood group antigens; encodes RhC and RhE antigens on a single polypeptide
On #1p36.11 adjacent to RH D gene
Rh (rhesus) blood group system is second most clinically significant blood group after ABO; is most polymorphic blood group, with variations due to deletions, gene conversions, and missense mutations
Rh antigens are carried by an oligomer of two major erythroid specific polypeptides, the Rh (D and CcEe) proteins and the RhAG glycoprotein; Rh proteins form a core complex critical to structure of erythrocyte membrane (Blood Rev 2006;20:93); may play a role in ammonia transport (J Biol Chem 2002;277:12499, but see Transfus Clin Biol 2006;13:132)
Discrepant or doubtful serologic results can be resolved by PCR-SSP technique (Transfusion 2007;47:54S)
Rarely causes hemolytic disease of newborn (Transfus Med 2000;10:305)
Uses: blood typing
Positive staining (normal): erythroid cells
References: Blood Group Antigen Gene Mutation Database, Blood 2000;95:375, OMIM 111700
CD240 D
Also called RH30 D, Rh blood group D blood group antigen; is major antigen of the Rh system
On #1p36.11 adjacent to RHCE gene
Rh (rhesus) blood group system is second most clinically significant blood group after ABO; is most polymorphic blood group, with variations due to deletions, gene conversions, and missense mutations
Weak D, formerly called D(u), occurs in 0.2 to 1% of whites; exhibits reduced expression of D antigen (Blood 1999;93:385); should not be labeled as Rh negative (Curr Opin Hematol 2006;13:476)
Individuals are classified as Rh positive or negative based on presence or absence of highly immunogenic D antigen on red cell surface
May have arisen historically by duplication of RHCE gene (Blood 2002;99:2272)
Discrepant or doubtful serologic results can be resolved by PCR-SSP technique (Transfusion 2007;47:54S)
Hemolytic disease of fetus and newborn: usually due to Rh negative woman whose partner is Rh+ or heterozygous and fetus is Rh+; woman has preexisting anti-RhD antibodies that cross placenta and harm fetus (Immunohematol 2006;22:188)
Can use maternal plasma in alloimmunized pregnancies to determine fetal RhD status (Fetal Diagn Ther 2006;21:404), or for RHD and RHCE genotyping (Prenat Diagn 2005;25:1079); genotyping from amniotic fluid or chorionic villi sampling was performed in past, but is more invasive (N Engl J Med 1998;339:1734, Clin Exp Med 2002;2:77)
Rh positive mothers may rarely (0.15%) develop new antibodies (other than anti-RHD) in third trimester, but no clinical significance (J Matern Fetal Neonatal Med 2007;20:59)
Having Rh negative mother may be risk factor for autistic children, due to use of mercury containing Rho-immune globulin (J Matern Fetal Neonatal Med 2007;20:385)
Uses: blood typing
Positive staining (normal): erythroid cells
References: Blood Group Antigen Gene Mutation Database, OMIM 111680, Wikipedia, eMedicine (Rh incompatibility)
CD240 DCE
Rh30D/CE crossreactive monoclonal antibodies
Uses: blood typing
Positive staining (normal): erythroid cells of normal Rh types
Negative staining: Rh null erythrocytes
References: Washington State University
Also called RH50 glycoprotein, RHAG, Rhesus blood group associated glycoprotein
Located at #6p21.1-p11
Is a strictly required posttranscriptional factor regulating Rh membrane expression (Blood 2002;100:1038)
Also appears to be an ammonium transporter (Proc Natl Acad Sci USA 2004;101:17222) and a CO2 channel (FASEB J 2007 Aug 21; [Epub ahead of print])
Defects cause Rh-null phenotype (OMIM 268150), associated with a chronic hemolytic anemia and spherostomatocytosis (J Biol Chem 1998;273:2207)
Uses: blood typing
Positive staining (normal): erythroid cells
References: OMIM 180297
Also called intercellular adhesion molecule 4 (ICAM-4), Landsteiner-Wiener (LW) blood group protein
Discovered with antibody raised in guinea pigs injected with the cells of rhesus monkeys, but Rh designation had already been taken
Binds to CD11a/CD18, CD11b/CD18 and CD11c/CD18 (Blood 2007;109:802)
May be critical in erythroblastic island formation, where erythroid progenitors differentiate (Blood 2006;108:2064)
May be ligand for platelet-activated alpha IIb beta 3 integrin (J Biol Chem 2003;278:4892)
In sickle cell disease, contributes to red cell-endothelial cell adhesion and vasoocclusion (Transfus Clin Biol 2006;13:44)
Uses: no significant clinical use by pathologists
Positive staining (normal): erythroid cells
References: Blood Group Antigen Gene Mutation Database, OMIM 111250
Also called MDR-1 gene (multidrug resistance to cancer), P glycoprotein 170 (molecular weight is 170K), ABCB1, P-binding cassette subfamily B member 1
Member of large superfamily of highly conserved ATP binding cassette transport proteins
"Detoxifying agent" that pumps toxins / drugs out of cells, also transports steroid hormones and transports substances across blood-brain barrier
Regulated by Y-box binding protein 1 (Clin Cancer Res 1998;4:2273)
May regulate cholesterol trafficking in cells (Proc Natl Acad Sci USA 2002;99:10347)
Levels reduced in inflamed intestinal epithelium of patients with GI disorders (Inflamm Bowel Dis 2007;13:710)
Specific polymorphisms affect gene expression and mRNA processing (AAPS J 2006;8:E515)
Specific polymorphism associations: ulcerative colitis (Hum Mol Genet 2006;15:797), Parkinson’s disease-reduced risk (Arch Neurol 2005;62:460); response to chemotherapy in small cell lung cancer (Jpn J Clin Oncol 2006;36:137)
MDR1 expression is poor prognostic factor in these malignancies: acute lymphoblastic leukemia - childhood (Oncol Rep 2004;12:1201) and adult types (Blood 2002;100:974), acute myelogenous leukemia-CD34 related coexpression of MDR1 and BCRP in patients age 60+ years (Ann Hematol 2007;86:329), acute promyelocytic leukemia in relapse (Haematologica 2002;87:1109), hepatocellular carcinoma-response to chemotherapy (World J Gastroenterol 2006;12:868), HIV related non-Hodgkin’s lymphoma (Pathol Res Pract 2007;203:1), lung and ovarian carcinoma (J Natl Cancer Inst 1992;84:1486), melanoma of uvea (Hum Path 1998;29:594), nasopharyngeal carcinoma (Hum Path 2001;32:1240), neuroblastoma (N Engl J Med 1991;325:1608), osteosarcoma (Int J Oncol 2006;29:1459), renal cell carcinoma (BMC Cancer 2006;6:293), soft tissue carcinoma-all ages (Hum Path 2005;36:994) and in children (J Clin Oncol 1990;8:689), Wilm’s tumor-staining of endothelial cells (AJCP 2002;117:484)
Uses: prognostic value in malignancies (see above)
Positive staining (normal): adrenal cortex (Acta Pathol Jpn 1990;40:545), brain endothelium (Exp Biol Med (Maywood) 2005;230:118), bronchi (Eur Respir J 1997;10:1837), duodenum-lateral and apical surfaces (Drug Metab Dispos 2005;33:1603), heart-vascular endothelium (J Histochem Cytochem 2002;50:1351), kidney-proximal tubules (Nephron 1997;77:284), liver-bile canaliculi (Arch Otolaryngol Head Neck Surg 1993;119:753), lung (J Clin Pathol 2002;55:332), lung-type I alveolar epithelium (J Pharmacol Exp Ther 2003;304:441), lymphocytes-CD4+ (Blood 1992;80:2735), placenta, retina (Mol Vis 2002;8:422), testicular endothelium, white blood cells (Blood 1994;83:2451)
Positive staining (disease): AML-M6 (Mod Path 2000;13:407), drug-resistant epileptic human brain (BMC Med 2004 Oct 9;2:37); see also malignancies above under “MDR1 expression is poor prognostic factor”
Micro images: normal - duodenum (fig C/D); heart (NF=nonfailing/normal heart); lung #1 (fig 1A); #2 (fig D/E); nasal mucosa (fig 1C); retinal pigment epithelium
carcinoma - bladder; breast #1; #2 (fig 1-7); #3 (fig D); #4-pre- (fig C) and post-chemotherapy (fig D); #5 (fig 2); gallbladder (fig 2); hepatocellular carcinoma #1; #2 (globular intracytoplasmic staining); #3 (fig 1A); pituitary adenoma (fig 2); renal cell; retinoblastoma #1; #2 (cytoplasmic staining); immunofluorescence
References: OMIM 171050, Oncogene 2003;22:7468, Wikipedia
Also called Natural Killer cell receptor 2B4
Regulates NK and T cell function in multiple ways (J Immunol 2005;175:2045)
Coexpression of 2B4 and CD160 defines a CD8+ T lymphocyte subpopulation with high cytolytic effector activity (Eur J Immunol 2006;36:2359)
Binds to CD48 (J Immunol 2006;176:4646), and CD244-CD48 interactions prevent NK cells from killing each other (Blood 2007;110:2020)
Functional changes are associated with X linked lymphoproliferative disease (J Exp Med 2000;192:337, J Immunol 2000;165:2932)
Diagrams: NK cell receptors
Uses: no significant clinical use by pathologists
Positive staining (normal): NK cells, CD8+ T cells, monocytes and basophils (Eur J Immunol 1999;29:1676), eosinophils (J Immunol 2005;174:110), spleen (Tissue Antigens 1999;54:27)
References: OMIM 605554
Also called p220/240
Very little information is available for CD245 directly; appears to be identical to NPAT (nuclear protein, ataxia-telangiectasia locus)
NPAT links S phase cyclin E/Cdk2 kinase activity to replication-dependent histone gene transcription (Biochemistry 2006;45:15915, Mol Cell Biol 2005;25:6140)
Uses: no significant clinical use by pathologists
Positive staining (normal): T cells (some), other white blood cells with varying intensity (Washington State Univ)
Also called ALK or ALK-1
Anaplastic lymphoma kinase gene at 2p23
Is NOT the same as Ki-1/CD30, as indicated by some references
Membrane spanning tyrosine kinase receptor; ligand is growth factor pleiotrophin
Normally expressed in developing nervous system and weakly in adult nervous system
In anaplastic large cell lymphoma, is usually fused with NPM (nucleophosmin) gene via t(2;5)(p23;q35), but also variants (Genes Chromosomes Cancer 2002;34:354)
ALK negative cases of primary anaplastic large cell lymphoma are associated with trisomy 2 (Mod Path 2005;18:235), consensus criteria for diagnosis are lacking (AJCP 2007;127:707)
ALK mutation causes hereditary hemorrhagic telangiectasia type 2 (J Dent Res 2006;85:705)
Prognostic significance: ALK+ tumors have favorable prognostic significance in anaplastic large cell lymphomas [ALCL] (Blood 1999;93:3913), including primary CNS ALCL (AJSP 2003;27:487) and inflammatory myofibroblastic tumors (AJSP 2007;31:509)
Interpretation: usually cytoplasmic and nuclear staining
Uses: prognostic value in anaplastic large cell lymphoma and inflammatory myofibroblastic tumor (see above), differentiate inflammatory myofibroblastic tumor (ALK+) from ALK negative spindled neoplasms in soft tissue (AJSP 2001;25:1364) and bladder (Mod Path 2007;20:592)
Positive staining (normal): embryonic neurons of CNS/PNS; weakly positive in adult brain
Positive staining (tumors): T/null cell anaplastic lymphomas (most), inflammatory myofibroblastic tumor (AJSP 2001;25:1364, AJSP 2001;25:761); diffuse large B cell lymphoma (rarely, Mod Path 2007;20:310); low level expression in some rhabdomyosarcomas, lipogenic tumors, Ewing’s/PNET, MFH, leiomyosarcoma and other soft tissue tumors (Hum Path 2004;35:711)
Negative staining: fibromatosis, GIST, nodular fasciitis, normal lymphoid tissue
Micro images: alveolar rhabdomyosarcoma (dot-like cytoplasmic staining-fig B); anaplastic lymphoma (fig C); anaplastic lymphoma-various images #1; #2; #3 (quality control); diffuse large B cell lymphoma (fig B); inflammatory myofibroblastic tumor #1 of bladder (fig d); #2 of abdomen (fig 2A); #3 of larynx (fig 2c); #4-site unspecified (fig B); #5-site unspecified (fig A); neuroblastoma (weak)
References: OMIM 105590
Also called T cell receptor zeta chain
Forms T cell-CD3 receptor complex with TCR alpha/beta and gamma/delta heterodimers and CD3-gamma, delta and epsilon (Proc Natl Acad Sci USA 1988;85:9709)
Couples antigen recognition to several intracellular signal transduction pathways; low expression causes impaired immune response
Low expression in tumor infiltrating T cells in various disorders - cancer of kidney (Cancer Invest 2004;22:871) and stomach (Cancer 2002;94:1437), Hodgkin’s lymphoma (Blood 1996;88:236); also active tuberculosis (J Infect Dis 2006;194:1385), systemic lupus erythematosus (J Immunol 2002;169:6048, Adv Med Sci 2006;51:181), normal pregnancy but not preeclampsia (Am J Obstet Gynecol 2003;189:843)
Defects cause primary T-cell immunodeficiency (OMIM 610163)
Diagrams: T cell activation
Uses: no significant clinical use by pathologists
Positive staining (normal): T cells
Micro images: gastric carcinoma intratumoral lymphocytes compared to CD3 epsilon (fig A): #1-normal expression (fig B); #2-reduced expression (fig B)
References: OMIM 186780
Also called endosialin, tumor endothelial marker 1 (TEM1)
Cell surface glycoprotein associated with tumors - traditionally thought present in vascular endothelial cells (Proc Natl Acad Sci USA 1992;89:10832, J Biol Chem 2001;276:7408), but may actually be marker of stromal fibroblasts (FEBS Lett 2005;579:2569)
Not present (or weak) in non-tumor associated endothelium
Uses: no significant clinical use by pathologists
Positive staining (normal): endometrium; embryos (Cancer Res 2001;61:6649), fibroblasts and pericytes during lymphoid tissue development (FEBS Lett 2007;581:3550); RNA at low/moderate levels in many organs
Positive staining (disease): MFH and other sarcomas, some capillaries and fibroblasts in carcinomas; endothelium of high grade brain tumors (J Neuropathol Exp Neurol 2004;63:1274); RNA at low/moderate levels in carcinomas (Cancer Immun 2005 Aug 3;5:10)
Micro images: normal tissue; normal colon and colorectal carcinoma (see TEM1); various tumors #1 (scroll down for color images); #2; #3
References: OMIM 606064
Also called ENPEP, glutamyl aminopeptidase, differentiation antigen gp160, aminopeptidase A
Regulates blood pressure via renin-angiotensin system (J Biol Chem 2006;281:23503)
Uses: no significant clinical use by pathologists
Positive staining (normal): kidney; also brain, heart, liver, lung, placenta, skeletal muscle, pancreas (Genomics 1993;17:657)
Positive staining (disease): cervical neoplasia (Lab Invest 2004;84:639), renal cell carcinoma-some (Proc Natl Acad Sci USA 1993;90:7069)
Micro images: cervical HSIL and squamous cell carcinoma
References: OMIM 138297
Programmed cell death ligand 2; also called B7DC
Involved in the costimulatory signal, essential for T lymphocyte proliferation and interferon gamma production
Found in the plasma membrane
Programmed cell death ligand 1; also called B7-H1
Involved in the costimulatory signal, essential for T lymphocyte proliferation and production of interferon gamma and IL10
Found in the plasma membrane and intracellular membrane
Also called ICOS
Enhances basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, upregulation of molecules that mediate cell-cell interaction and effective help for antibody secretion by B-cells. Essential both for efficient interaction between T and B-cells and for normal antibody responses to T-cell dependent antigens. Plays a critical role in CD40-mediated class switching of immunoglobin isotypes
A type I membrane protein
Defects cause ICOS deficiency (MIM:607594), a form of common variable immunodeficiency characterized by recurrent bacterial infections of the respiratory and digestive tracts, but without splenomegaly, autoimmune disease, sarcoid-like granulomas, overt T cell immunodeficiency
Present in: activated T cells, tonsillar T cells, fetal and newborn thymic medulla
References: Swiss-Prot entry