CD Markers CD50 to CD99
Last revised 17 June 2009
Last major update November 2006
Copyright © 2001-2009 PathologyOutlines.com, Inc.
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CD50 to CD99
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Primary references
American
Journal of Clinical Pathology (AJCP), August 1975 to November 2006
American Journal of Surgical Pathology (AJSP), March 1977 to November 2006
Archives of Pathology and Lab
Medicine (Archives), January 1976 to September
2006
Human
Pathology (Hum
Path), March 1970 to November
2006
Modern Pathology (Mod Path), January
1988 to November 2006
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
Also known as ICAM-3, the third
counter receptor for LFA-1 (CD54)
Provides adhesion signals important
in B-T cell interactions and regulates leukocyte morphology
May predict resistance to radiation
therapy in cervical cancer (Int
J Cancer 2005;117:194)
Costimulator for HIV1 replication (J Virol 2004;78:6692, J Virol 2002;76:32)
Uses: no significant clinical use by
pathologists
Positive staining (normal): leukocytes including eosinophils
(J
Allergy Clin Immunol 2003;111:1024) and mast cells (Cell
Adhes Commun 1999;7:195), epidermal Langerhans cells (J
Invest Dermatol 1995;104:995), endothelial cells (J
Vasc Res 2004;41:28)
Positive staining (disease): synovium in rheumatoid arthritis (Arthritis
Rheum 2003;48:360)
Negative staining: non-hematopoietic cells, platelets
(J Clin Invest 1994;94:1243)
References: OMIM 146631
Also called integrin alpha chain V
or vitronectin receptor-alpha chain
Integrins are membrane receptors for extracellular
matrix-mediated cell adhesion and migration, cytoskeletal organization, cell
proliferation, cell survival and differentiation
Integrins are composed of an alpha chain and a beta chain
Alpha-V integrins are a subset of integrins with a common
alpha-V subunit combined with beta subunits 1, 3, 5, 6 or 8
The beta chain of the vitronectin
receptor is CD61
Most alpha-V integrins recognize the RGD (Arg-Gly-Asp)
sequence in various ligands such as vitronectin, fibronectin, osteopontin, bone
sialoprotein, thrombospondin, fibrinogen, von Willebrand factor, tenascin or
agrin
Alpha V beta 3 integrin may mediate
melanoma progression (Oncogene
2005;24:4710)
CD51 on some dendritic cells serves as adenovirus
receptor (J
Leukoc Biol 2006;79:1271)
Uses: no significant clinical use by
pathologists
Positive staining (normal): endothelial cells, megakaryocytes,
osteoclasts (Histochemistry
1991;96:169), monocytes and macrophages,
placenta cytotrophoblast and Hofbauer cells (Acta
Histochem 2003;105:253), fibroblasts
Positive staining (disease): osteoclast disorders including
osteoclast-like giant cell neoplasms (Mod
Path 2006;19:161)
and inflamed synovium (Ann
Rheum Dis 1993;52:182)
Negative staining: cartilage (Ann Rheum Dis 2000;59:448)
References: OMIM 193210
Also called Campath-1 and epididymal
secretory protein E5
CD52 antibodies are lytic for target
cells, both with human complement and via antibody dependent cellular
cytotoxicity
Uses: antibodies (Alemtuzumab) are used for long-term
depletion of T lymphocytes from donor marrow to prevent graft versus host
disease (Bone
Marrow Transplant 2000;26:69, Transplantation
1999;67:620); also to treat refractory CLL; high serum levels are poor prognostic
marker in CLL (Cancer
2004;101:999); may treat other malignancies (see CD52+ disorders below), including
pure red blood cell aplasia (Br
J Haematol 2003;123:278); differentiates eosinophils (CD52++) from
neutrophils (CD52 weak/negative)
Micro images: figures
1A/B: normal tonsil shows lymphocytic staining, but there is no staining of
connective tissue or vessels; C: follicular lymphoma is CD52+; D:
Reed-Sternberg cells (arrows) are CD52-;
figures
2A/B: SLL/CLL is CD52+; C: anaplastic lymphoma is CD52+; D: adult T cell
leukemia/lymphoma is CD52+
Positive staining (normal): thymocytes, lymphocytes,
monocytes/macrophages, eosinophils, mast cells (Clin
Lymphoma Myeloma 2006;6:478), epithelial cells lining the male reproductive tract
Positive staining (disease): most lymphoid malignancies
(variable levels, J Clin Path 1994;47:313), including lymphoplasmacytic
lymphoma (100%, AJCP
2005;124:414),
myeloma (5-10%, AJCP
2004;121:482),
hairy cell leukemia (Am
J Hematol 2003;74:227); T cell large granular lymphocytic leukemia (Leuk
Lymphoma 2005;46:723), Langerhans cell histiocytosis (Pediatr
Blood Cancer 2005;44:251)
Negative staining: neutrophils, Langerhans cells
(normal), lymphocytes in paroxysmal nocturnal hemaglobinuria, Reed-Sternberg
cells in Hodgkin’s lymphoma
References: OMIM 114280
Most specific and reliable
pan-leukocyte marker
Encodes member of tetraspanin
family, a cell surface protein with 4 hydrophobic domains that mediate signal
transduction
Also has adhesion/activation
functions
Upregulated in macrophages exposed
to lipopolysaccharide (Mol Cells 2004;17:125)
May transduce CD2-generated signals
in T cells and natural killer cells
May be a thymocyte selection marker,
with CD69 (Int Immunol 2002;14:249)
Familial deficiency is associated
with recurrent infectious diseases (Clin Diagn Lab Immunol 1997;4:229)
Uses: no significant clinical use by
pathologists
Positive staining (normal): leukocytes; also dendritic cells,
osteoclasts and osteoblasts, mesangial cells (Kidney
Int 2003;63:534)
Positive staining (disease): radioresistant tumor cells
Negative staining: platelets, red blood cells,
non-hematopoietic cells
References: OMIM 151525
Also called ICAM-1 (intercellular
adhesion molecule 1)
Ligand for LFA-1 (CD50)
Receptor for rhinovirus (Proc Natl Acad Sci USA 1991;88:7993),
malaria infected erythrocytes (Infect Immun 2006;74:3262,
Proc Natl Acad Sci USA 2000;97:1766)
Involved in adhesion of neutrophils
to endothelium at site of inflammation
Reacts with CD11a / CD18 or CD11b /
CD18 resulting in immune reaction or inflammation
Reduced expression in endometrial
cells may contribute to endometriosis (Immunol
Lett 2002;80:49)
Uses: CD54 negative gastric carcinoma cells may predict
nodal metastases (Dig
Dis Sci 2005;50:2224); low CD54 levels associated with poor prognosis in
childhood ALL (Br
J Biomed Sci 2003;60:149)
Micro images (Mod Path subscribers): keratoacanthoma; poorly
differentiated squamous cell carcinoma
Positive staining (normal): broad, B and T cells and B cell
precursors, monocytes, osteoclasts, endothelial cells, epithelial cells
(various)
Positive staining (tumors): keratoacanthoma (more in fully
developed lesions with inflammatory infiltrate), cutaneous squamous cell
carcinoma (focal if well differentiated, intense if poorly differentiated, Mod
Path 2003;16:8)
Negative staining (tumors): intravascular B cell lymphoma
References: OMIM 147840
Also called complement decay
accelerating factor (DAF)
Gene encodes Cromer blood group (Blood
Group Antigen Gene Mutation Database)
Binds C3bBb (alternative pathway
convertase) and C4b2a (classical pathway convertase) to accelerate decay of the
C3 convertases; protects against inappropriate complement activation (J Biol Chem 2005;280:2569)
Receptor for CD97, echovirus (Proc Natl Acad Sci USA
2002;99:10325) and Coxsackie B virus (J Virol 1998;72:9407)
Also is part of
lipopolysaccharide-induced receptor complex (Eur
J Immunol 2003;33:1399)
Genetic defects that cause a
reduction or loss of both CD59 and CD55 on erythrocytes produce paroxysmal
nocturnal hemoglobinuria (PNH); also cause defective platelets, granulocytes,
erythrocytes and possibly lymphocytes
CD55 deficiency is common in
patients treated with Campath (anti-CD52), which may predispose to PNH (Transplant
Proc 2006;38:1750)
A minor population of CD55-CD59
negative granulocytes and red blood cells predicts a good response to
immunosuppressive therapy in patients with acquired aplastic anemia (Blood
2006;107:1308)
Loss of CD55 is associated with poor prognosis in
breast cancer (Clin Cancer Res 2004;10:2797); however high expression is associated with poor
prognosis in colorectal carcinoma (Cancer
Immunol Immunother 2003;52:638)
Case reports: pregnant woman with
thrombocytopenia due to PNH
Uses:
diagnosis of PNH (AJCP
2006;126:781)
Micro images: breast
carcinoma staining #1; #2; #3
Positive staining (normal): all hematopoietic cells and all
cell types in intimate contact with complement proteins; also epithelial cells
lining extracellular compartments, body fluids, extracellular matrix
References: OMIM 125240
Also called N-CAM (neural cell
adhesion molecule)
Nerves: regulates homophilic (like-like)
interactions between neurons and between neurons and muscle; associates with
fibroblast growth factor receptor and stimulates tyrosine kinase activity of
receptor to induce neurite outgrowth; when neural crest cells stop making N-CAM
and N-cadherin, and start displaying integrin receptors, cells separate and
migrate (Cell Sci 2002;115:283)
Hematopoiesis: prototypic marker of NK cells, also
present on subset of CD4+ and CD8+ T cells
Adhesion: contributes to cell-cell or
cell-matrix adhesion during development
Prognostic factor: CD56 negative myeloma has poor
prognosis (Leuk
Lymphoma 2004;45:61)
Case reports: 6 year old girl with B-ALL and CD56
and CD57 coexpression (Pediatr
Hematol Oncol 2004;21:677), CD56+ plasma cell leukemia
Uses: marker for NK cells and NK lymphomas; differentiates
plasma cells in myeloma (CD56+) from reactive plasmacytosis or MGUS (CD56-, Am J Path 2002;160:1293);
detect neuroendocrine disorders (J Clin Path 2002;55:535), particularly if extensive crush
artifact (J
Clin Path 2005;58:978), defines cutaneous lymphoproliferative disorders
with poor prognosis, other than cutaneous T cell lymphoma (J
Clin Pathol 2007;60:981)
Micro images: osteoblasts; MPNST; plasma cells in myelomas
with lytic lesions (CD56+) versus other disorders (CD56-); pancreatic endocrine
neoplasm vs. solid-pseudopapillary tumor (both are CD56+); nasal
cavity (figure 1E)
NK lymphomas - nasal type
- nasal
cavity; testes
(figure 3C)
other lymphomas - blastic
NK lymphoma (figure 3); blastoid
NK lymphoma (figure 5); CD56+ intestinal
T cell lymphoma (figure 1); NK-like
T cell lymphoma of ileum (figure 4)
Flow cytometry images: coexpression of CD56
and CD138 in plasma cell leukemia (not typical); small
cell carcinoma of nasal cavity (figure 1D)
Positive staining (normal): NK cells (80-90%), large granular
lymphocytes, activated T cells, osteoblasts; cerebellum and cortex at
neuromuscular junctions, neuroendocrine tissue and neurons (membranous
pattern), glia; skeletal muscle
Positive staining (disease) - leukemia/lymphoma
- acute myeloid leukemia (some), cutaneous lymphoproliferative disorders, granulocytic
sarcoma (variable), myeloma, NK/T cell lymphomas, T
cell lymphomas (various)
Positive staining (disease): other
- cardiac ischemic damage (Verh
Dtsch Ges Path 2004;88:246), extrahepatic biliary atresia (AJSP
2003;27:1454),
Merkel
cell carcinoma (J
Dermatol Sci 2003;31:219), mesotheliomas (some), neuroblastoma (adult), neuroendocrine
carcinomas (AJSP
2006;30:684),
pancreatic
acinar cell carcinoma, pancreatic solid pseudopapillary tumor (Mod
Path 2006;19:1409),
pheochromocytoma,
small cell carcinoma of cervix (Int
J Gynecol Path 2005;24:113), small cell
carcinoma of lung and prostate
(AJSP
2006;30:705), sustentacular cell tumor (AJSP
2006;30:268),
synovial sarcoma (usually, Mod
Path 2006;19:659),
thyroid carcinoma (AJCP
2003;120:64), Wilm’s tumor
Negative staining: granulocytes, monocytes, B cells;
ALL, large granular NK cell lymphocytosis, (some cases, Am J Path 2004;165:1117), plasma cell leukemia,
PNET/Ewing’s sarcoma
References: OMIM 116930
Also called Leu7,
beta-1,3-glucuronyltransferase 1, glucuronosyltransferase P
Glycoprotein with cell adhesion
functions
May define a
phenotype associated with replicative senescence in HIV specific CD8+ T cells (Blood 2003;101:2711)
Case reports: 6 year old girl with B-ALL and CD56
and CD57 coexpression (Pediatr
Hematol Oncol 2004;21:677)
Uses: marker of NK cells and neuroendocrine tumors, helps
distinguish high grade prostatic adenocarcinoma (CD57+) from high grade
urothelial carcinoma (CD57-)
Micro images: metanephric
adenoma (figure E); large granular lymphocytic
leukemia
Positive staining (normal): NK subset, T cell subset,
neuroectodermal tissue, retina, brain, prostate, renal proximal tubules
Positive staining (disease): leukemia/lymphomas
- autoimmune
lymphoproliferative syndrome, hepatosplenic T cell lymphoma (some),
nodular lymphocyte predominant Hodgkin lymphoma (CD57+ rosettes in 50%, AJCP
2003;119:192), pre T-ALL (occasional), T-cell large granular
lymphocytic leukemia (some)
nerve sheath origin
lesions -
benign epithelioid nerve sheath tumor (AJSP
2005;29:39),
chordoma, dendritic cell neurofibroma with pseudorosettes (AJSP
2001;25:587), melanotic
neuroectodermal tumor of infancy, MPNST (expression decreases with tumor
grade, AJSP
2003;27:1337),
nerve
sheath myxoma (AJSP
2005;29:1615),
Positive staining (tumors): other - carcinoid tumors, desmoplastic nested spindle cell
tumor of liver (AJSP
2005;29:1),
desmoplastic small round cell tumor (AJSP
1998;22:1314),
germ cell tumor (embryonal carcinoma, seminoma), mesenchymal chondrosarcoma, metanephric adenoma (AJSP
2001;25:1290), neuroendocrine carcinoma of prostate (AJSP
2006;30:684)
and other sites, PNET, prostatic adenocarcinoma, renal carcinoid, renal clear cell
carcinoma (some), small cell carcinoma of lung and other sites, spindle cell
thymoma (AJSP
2001;25:111), synovial sarcoma, thyroid papillary carcinoma (Cancer
2006;108:331)
Negative staining: B cells, monocytes, red blood
cells, platelets; NK/T cell lymphoma-nasal type, Wilm’s tumor
References: OMIM
151290
Also called LFA-3 (lymphocyte
function associated antigen)
Ligand for CD2 (J
Mol Biol 2001;312:711)
Mediates adhesion between NK cells
and target cells (J Immunol 2003;170:294), antigen presenting cells and T cells (Cell
1999;97:791), thymocytes and thymic epithelial
cells
High serum levels in Hepatitis B,
associated with liver cell damage (World J Gastroenterol 2006;12:4237)
Uses:
detect minimal residual disease in pre-B ALL (Haematologica 2003;88:1245)
Micro images: various
images; lymphoma
(type unknown)
Positive staining (normal): leukocytes (but not mature B
cells), pre B cells, erythrocytes, endothelial cells, epithelial cells,
fibroblasts, cardiac muscle (J Clin Path 1990;43:893)
Positive staining (disease): pre-B ALL (AJCP
2005;123:119)
Negative staining: mature B cells
References: OMIM
153420
Also called protectin, complement
regulatory molecule
Regulates complement mediated cell
lysis by inhibiting formation of membrane attack complex (MAC); binds to C8 or
C9 components, preventing incorporation of multiple copies of C9 required for
complete formation of osmolytic core
Also makes cells susceptible to NK
cell mediated cytotoxicity (J
Immunol 2006;176:2915)
Genetic defects that reduce both
CD59 and CD55 on erythrocytes produce paroxysmal nocturnal hemoglobinuria
(PNH); also cause defective platelets, granulocytes, erythrocytes and possibly
lymphocytes
Low CD59 levels may also cause
PNH-like symptoms after Campath therapy (Transplant
Proc 2006;38:1750)
Not a particularly good marker for
detecting PNH+ monocytes (AJCP
2006;126:781)
In diabetes, glycation may inhibit
CD59, causing MAC deposition in vessels, leading to vascular complications (Diabetes 2004;53:2653)
Naegleria (Infect Immun 2006;74:1189), Borrelia (J Immunol 2003;170:3214) and HIV (J Gen Virol 1997;78:1907) may resist complement mediated lysis via a surface
CD59 like protein
Uses: no significant clinical use by
pathologists
Positive staining (normal): most cells
Positive staining (disease): squamous cell carcinoma of head and
neck (J
Oral Path Med 2006;35:560)
References: OMIM 107271
Use of CD60, CDw60 and CD60a, CD60b
and CD60c is inconsistent
Not proteins, but oligosaccharides
present on gangliosides
CD60a: GD3 - carbohydrate structure
CD60b: 9-O-acetyl-GD3 - carbohydrate
structure
CD60c: 7-O-acetyl-GD3 - carbohydrate
structure
Antibodies provide costimulatory
signals for T cells
Expressed on most T cells in
autoimmune lesions (Immunol
Invest 2001;30:67)
CD8+ CD60+ T cells may regulate IgE
memory responses and isotype switching (Hum
Immunol 2005;66:1029)
Associated with Th1 immune response in skin (Br
J Dermatol 2003;149:739)
Uses: no significant clinical use by
pathologists
Positive staining (normal): platelets, T cells (30%, Carbohydr
Res 2000;329:791), thymic epithelium, activated
keratinocytes, melanocytes, synovial fibroblasts, glomeruli, smooth muscle
cells, astrocytes; also epithelium of reproductive system, exocrine and
endocrine glands (Histochem
J 2000;32:447)
Positive staining (disease): T cells in rheumatoid arthritis and
psoriasis, monocytes in cutaneous T cell lymphoma (Acta
Derm Venereol 2001;81:263)
Negative staining: B cells, granulocytes, monocytes
References: glycolipids
CD60a
Not a protein: oligosaccharide
present on gangliosides
GD3 - carbohydrate structure
Uses: no significant clinical use by
pathologists
CD60b
Not a protein: oligosaccharide
present on gangliosides
9-O-acetyl-GD3 - carbohydrate structure
May protect tumor cells from
apoptosis (Int
J Cancer 2006;119:67)
Uses: no significant clinical use by
pathologists
Positive staining (disease): Leishmania promastigotes (Glycobiology
2003;13:351)
CD60c
Not a protein: oligosaccharide
present on gangliosides
7-O-acetyl-GD3 - carbohydrate
structure
Uses: no significant clinical use by
pathologists
Also called integrin beta 3 chain
Combines with CD41 (integrin alpha
IIb) to form platelet glycoprotein IIb/IIIa, a receptor for fibrinogen,
fibronectin, plasminogen, prothrombin, thrombospondin, vitronectin and von
Willebrand factor
Combines with CD51 to form receptor
for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin,
osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand
factor
CD51-CD61 is present on endothelium,
endothelial cells, smooth muscle, some B cells, monocytes, macrophages,
platelets, osteoclasts, mast cells, fibroblasts and tumor cells
Platelet activation causes a
conformation change in GPIIb/IIIa, enabling the binding of soluble fibrinogen
and forming a platelet plug
CD61 defects cause Glanzmann
thrombasthenia, an autosomal recessive disorder and the most common inherited
platelet disease
CD61 has role in pathogenesis of
asthma (Am J Respir Crit Care Med
2005;172:67)
Polymorphisms may cause premature coronary artery
disease (Archives 1999;123:1223)
High pre-kidney transplant levels associated with
acute rejection (Transplant
Proc 2003;35:1360)
Uses:
identify platelets, megakaryocytes, platelet thrombi; distinguish TTP (diffuse
CD61+ platelet rich thrombi) from DIC (no/sparse thrombi, Cardiovasc
Path 2005;14:150);
count platelets in thrombocytopenic patients (Br
J Haematol 2001;112:584)
Micro images: AML-M7 #1; #2; #3; #4; #5
(figures C, D); dysplastic megakaryocytes
#1; #2
Positive staining (normal): platelets, megakaryocytes, myeloid
progenitor cells, endothelial cells
Positive staining (disease): AML M7, AML M6 (some), blasts in
transient myeloproliferative disorder (AJCP
2001;116:204)
Negative staining: AML M0-M5, M6 (most)
References: J Clin Invest 2005;115:3363 (review),
OMIM 173470
Also called E selectin, endothelial
(leukocyte) adhesion molecule-1, ELAM1, SELE
Ligand for sialyl-Lewis X (CD15s);
also CD43 (Blood
2006;107:1421),
CD44 (J Exp Med 2005;201:1183), CD162/PSGL-1 (Am J Physiol Cell Physiol
2005;289:C415) and tumor cells (Cancer Res 2005;65:5750)
Inhibited by hCG (Anticancer
Res 2005;25:1811)
Mediates leukocyte rolling (causes
slow rolling, which may assist with adhesion) and adhesion to activated
endothelium at inflammatory sites
Also associated with
atherosclerosis, tumor cell adhesion during hematogenous metastasis (Cancer
Res 2006;66:9117)
Patients with Leukocyte Adhesion
Deficiency 2 syndrome (OMIM 266265), who lack sialyl Lewis X component
of selectin counter-receptors, suffer recurrent pyogenic infections
Homozygosity for Ser128Arg polymorphism associated
with recurrent venous thromboembolism (Arch
Intern Med 2006;166:1655) and myocardial infarction (Arterioscler Thromb Vasc Biol
2003;23:783), due to increased rolling and adhesion of neutrophils and
mononuclear cells, or alteration of lymphocytes binding to E selectin (J Immunol 2002;169:5860)
Other mutations also associated with vascular disease
(Brain
Res 2006;1108:221)
High serum levels associated with insulin resistance
in type 2 diabetes (Metabolism
2005;54:376),
vascular disease in type 1 diabetes (J
Diabetes Complications 2006;20:188), relapse in AML (Hematology
2002;7:83)
Cryptococcus induces WBC surface L-selectin shedding to
reduce WBC infiltration into infected tissues (J
Infect Dis 2005;191:1361)
Trypanosoma cruzi produces a mucin that,
through CD62L binding, inhibits T cell proliferation (Int
Immunol 2004;16:1365)
Uses: no significant clinical use by
pathologists
Micro images: normal
tonsil vessels; normal brain and
renal carcinoma; experimental acute
pancreatitis
Positive staining (normal): endothelium after cytokine
stimulation
Positive staining (disease): endothelium in chronic inflammatory
disorders of skin and synovium, hemangiomas (Am
J Path 1996;148:1181)
References: OMIM 131210
CD62L
Also called L selectin, LECAM-1,
SELL
Mediates lymphocyte homing to high
endothelial venules of peripheral lymphoid tissue, migration of lymphocytes to
inflamed tissue via leukocyte rolling on activated endothelium
Binds to CD34 (Adv
Exp Med Biol 1998;435:55)
High serum levels associated with
diabetic retinopathy (Ocul
Immunol Inflamm 2003;11:123), relapse in AML (Hematology
2002;7:83)
Reduced levels on T cells in neonatal pertussis (AJCP
2000;114:35)
Loss of expression is associated with progression of
low grade MALT (Mod
Path 2001;14:798)
Functionally active endothelial
L-selectin ligands cause lymphocyte infiltration into transplanted hearts at
the onset and during acute rejection episodes (Am J Path 1999;155:1303)
Uses: may distinguish lymphomatoid
hypersensitivity reactions from true endogenous T-cell dyscrasia (J
Cutan Pathol 2005;32:12)
Micro images: distribution
on neutrophil (confocal microscopy);
rat thymus
Positive staining (normal): B, T, NK cells (some), monocytes,
neutrophils, eosinophils, trophoblast (Science
2003;299:405),
epidermal Langerhans cells
References: OMIM 153240,
Am J Path 1999;155:1013, J Cell Mol Med 2005;9:255
CD62P
Also called P selectin, PADGEM, SELP
Interaction with CD162 mediates
tethering and rolling of leukocytes on the surface of activated endothelial
cells
Also (a) mediates delivery of
lymphocytes to high endothelial venules (with CD62L); (b) a platelet
alpha-granule membrane protein that redistributes to the plasma membrane during
platelet activation and degranulation; (c) has procoagulant activity (Trends
Mol Med 2004;10:179)
Constitutive expression in
inflammation may contribute to tissue destruction, atherogenesis and thrombosis
Reduced expression in gray platelet
syndrome (139090), advanced melanoma (Am
J Path 1998;152:679)
Increased expression in Takayasu's
arteritis (Circ J 2006;70:600)
Increased serum levels associated with
atherosclerosis (Eur Heart J 2003;24:2166)
Val640Leu polymorphism is
associated with thromboembolic stroke (Hum Mol Genet 2004;13:389)
Endothelial P-selectin has important
role in pathogenesis of cerebral malaria (Am J Path 2004;164:781)
Promotes metastases by tumor cell binding (Glycobiology
2007;17:185)
Uses:
distinguishing heparin-induced thrombocytopenia without and with
thrombosis (Thromb Haemost 1999;82:1255)
Micro images: megakaryocytes in bone
marrow #1; #2; #3; endothelial cell staining
in tonsillar tissue; expression in
mice infected with Plasmodium berghei;
expression
in rats with lung injury
Positive staining (normal): platelets, megakaryocytes,
activated endothelial cells (membranes of Weibel-Palade bodies)
Negative staining: sinusoidal endothelium (Am
J Path 1993;142:481)
References: OMIM
173610
Also called NKI-C3 (J
Natl Cancer Inst 1992;84:422), lysosomal membrane-associated glycoprotein 3, LAMP-3,
melanoma associated antigen, ME491
Member of tetraspanin superfamily of
integral membrane proteins - tetraspanins form lateral associations with
integrins and may act as organizers of multimolecular networks that modulate
integrin mediated signaling, cell morphology, motility and migration
Intracellular lysosomal / endosomal
/ granule protein, in Weibel-Palade bodies of endothelium and in azurophil
granules of neutrophils (Am
J Pathol 1994;144:1369)
Serves as adaptor protein that links
its interaction partners to the cell’s endocytic machinery (Proc Natl Acad Sci USA
2003;100:15560)
Marker of platelet activation that
is transported to surface after activation; also modulates platelet spreading
on immobilized fibrinogen (Thromb
Haemost 2005;93:311)
Associated with early stages of
melanoma progression (Cancer
Res 1988;48:2955)
Deficiency associated with
Hermansky-Pudlak syndrome (OMIM
203300)
High pre-kidney transplant levels are associated with
acute rejection (Transplant
Proc 2003;35:1360)
Used for basophil activation tests (Allergy
2006;61:1084)
CD63 pathway from host multivesicular bodies provides
essential lipids to Chlamydia to maintain productive intracellular infection (J Cell Sci 2006;119:350)
Uses:
marker of melanoma (although non-specific) and melanocytic tumors; may be
useful for other tumors (see below)
Micro images: cellular
neurothekeoma; Chlamydia inclusions
#1; #2; #3
Positive staining (normal): activated platelets, endothelium,
fibroblasts, macrophages, mast cells, osteoclasts; weakly expressed on B and T
cells and granulocytes; also bronchial glands, neural tissue (brain white
matter and peripheral nerves), nevi, salivary glands, smooth muscle, synovial lining
cells
Positive staining (tumors): angiomyolipoma (100%, Archives 2001;125:751), atypical fibroxanthoma (33%),
breast carcinoma (100%, Am J Pathol 1998;153:973), carcinoids (some), cellular
fibrous histiocytoma (50%), cellular neurothekeoma (81%, Mod
Path 2004;17:230),
clear
cell fibrous papule of nose (83%, Am
J Dermatopathol 2005;27:296), deciduoid mesothelioma (67%, AJSP
2000;24:285), dermatofibrosarcoma protuberans (90%, AJCP
1992;97:478),
histiocytic sarcoma, juvenile xanthogranuloma (60%), melanoma (90%), primitive
nonneural granular cell tumors of skin (90%, AJSP
2005;29:927),
renal
oncocytoma (apical and polar staining) and renal chromophobe
carcinoma-eosinophilic variant (diffuse staining, Virchows
Arch 2005;447:938),
reticulohistiocytoma
(50%), thyroid medullary carcinoma (some), xanthoma (80%)
Negative staining: epithelioid cell histiocytoma,
Langerhans cell histiocytosis
References: OMIM 155740, AJCP
2006;126:554
Also called Fc gamma RI
High affinity receptor binds to Fc
region of IgG
Important in phagocytosis via
receptor-mediated endocytosis of IgG-antigen complexes
Mediates antigen capture for
presentation to T cells, antibody-dependent cellular cytotoxicity, release of
cytokines and reactive oxygen intermediates
Also binds to C reaction protein and
mediates its effects (J Biol Chem 2005;280:25095)
Denge fever immune complexes enter
macrophages via CD64 (J
Virol 2006;80:10128)
Uses:
high neutrophil CD64 levels predict sepsis (Archives 2006;130:654,
Lab
Hematol 2005;11:137), early onset of infection in neonates (Pediatr Res 2004;56:796), infection in rheumatoid arthritis patients (J
Rheumatol 2006;33:2416)
Positive staining (normal): antigen presenting cells including
macrophages/monocytes, activated granulocytes, dendritic cells; also early
myeloid cells
Positive staining (disease): AML M3 (usually); M4, M5 (AJCP
1998;110:797),
M0-M2
(variable);
Negative staining: AML M7
Flow cytometry images: levels
in patient with elevated neutrophil CD64
References: OMIM 146760
Also called VIM2,
ceramide-dodecasaccharide, dimeric sialyl-CD15
Adhesive carbohydrate (not a
protein) that appears to be significant risk factor for extravascular AML
infiltration (Leuk
Res 2001;25:847)
Uses: myeloid antigen used in flow cytometry
Positive staining (normal): myeloid cells, monocytes
Negative staining: lymphocytes
Positive staining (disease): AML
CD65s
Also called sialylated-CD65
A carbohydrate antigen, not a
protein
Appears when CD34 antigen disappears
Antibodies may either recognize CD65s
(sialylated) or CD65 (non-sialylated)
Uses: for acute leukemia cell typing and to identify a
subset of pre-pre-B ALL (AJCP
2002;117:380)
Positive staining (normal): granulocytes, monocytes
Positive staining (disease): myeloid leukemia, low levels in AML
M0-M1 (Leukemia
2003;17:1544)
Also called CEACAM1, biliary
glycoprotein, BGP, C-CAM
Primordial protein of
carcinoembryonic antigen (CEA) family
Cell adhesion molecule capable of
activating neutrophils
Receptor for Neisseria
gonorrhoeae and N. meningitides;
binding prevents epithelial detachment, a defense mechanism that hinders
colonization (J Cell Biol 2005;170:825); CD66a+ B cells are also killed by N. gonorrhoeae (Infect Immun 2005;73:4171)
With osteopontin, may mediate invasion of
extravillous trophoblast at maternal-fetal interface (J Clin Endocrinol Metab
2005;90:5407)
Interactions with CEA inhibit NK cell cytotoxicity (J Immunol 2005;174:6692)
Downregulated in breast (J Histochem
Cytochem 1997;45:957), colorectal,
endometrial, hepatocellular, prostate (particularly Gleason grade 4/5, Hum
Path 2002;33:290) and renal cell carcinoma (J
Pathol 2004;204:258)
Uses: expression predicts metastases in cutaneous melanoma
(J Clin Oncol 2002;20:2530)
Micro images: cutaneous melanoma; metastatic melanoma; expression at maternal-fetal
surface; various breast lesions; colon; rectum
Positive staining (normal): granulocytes, lymphocytes,
epithelial cells, endothelial cells, prostate glands and ducts (dense), bile
canaliculi between liver cells, extravillous trophoblast (Am J Pathol 2000;156:1165)
Positive staining (disease): low grade prostate carcinoma
Negative staining: high grade (Gleason 4/5) prostate
carcinoma
References: OMIM 109770
CD66b
Also called CEACAM8. NCA-95, CGM6;
formerly CD67
Cell adhesion molecule capable of
activating neutrophils
Increased expression on peripheral
blood neutrophils and eosinophils of rheumatoid arthritis patients (Scand
J Immunol 1999;50:433)
Uses:
marker for granulocytes
Micro images: neutrophils
adhering to infracted cardiomyocytes
Positive staining (normal): granulocytes
Positive staining (disease): chronic myelogenous leukemia (Cancer
Res 1990;50:6534),
cardiomyocytes in areas of infarction (Cardiovasc
Res 1999;41:603)
CD66c
Also called nonspecific cross
reactive antigen, CEACAM6, NCA 50/90
Cell adhesion molecule capable of
activating neutrophils
Uses: no significant clinical use by
pathologists
Positive staining (normal): granulocytes
Positive staining (disease): ALL (43%, BMC Cancer 2005;5:38)
References: OMIM
163980
CD66d
Also called CEACAM3, CGM1
Cell adhesion molecule capable of
activating neutrophils
Has important role in control of
pathogens by the innate
(opsonin-independent) immune system (J Exp Med 2004;199:35)
Used by Neisseria. gonorrhoeae, Moraxella catarrhalis,
and Hemophilus influenzae to anchor themselves to and invade host cells
N. gonorrheae has an opacity-associated (Opa)
protein that binds to CEACAM3 (J Biol Chem 2001;276:17413)
Uses: no significant clinical use by
pathologists
Positive staining (normal): granulocytes
References: OMIM 609142
Also called CEA, carcinoembryonic
antigen, CEACAM5
Either polyclonal (pCEA) or
monoclonal (mCEA)
Normally detected
in glycocalyx of fetal epithelial cells
May play a role in the metastasis of
cancer cells
Usually considered an epithelial
marker with strong staining in adenocarcinomas
Case reports: CEA immunostaining in benign
multicystic mesothelioma of the peritoneum (not typical, Archives 2001;125:944)
Uses:
Colorectal carcinoma: monitor serum levels (elevated in
72-97%) to detect recurrence (World J Gastroenterol 2006;12:3891), elevated preoperative serum
levels are poor prognostic factor (Int
J Cancer 2002;101:545); caution - elevated levels also present in
cirrhosis, biliary obstruction, hepatitis, inflammatory bowel disease, smokers,
post-surgical bowel sequestration with mucocele (Archives 2003;127:1376)
Adenocarcinoma
(lung) vs. epithelioid mesothelioma: monoclonal CEA is 97% specific for lung
adenocarcinoma (Histopathology
2006;48:223); exhibits diffuse cytoplasmic
staining with membrane enhancement in adenocarcinoma, negative in mesothelioma
Adenocarcinoma
(lung) vs. reactive mesothelial cells in fluid cytology: positive staining is 76% sensitive
(AJCP
2001;116:709)
Breast
cancer vs. benign breast disease in FNA fluid: high
levels are suggestive of malignancy (Archives 2004;128:1251)
Cysts
(various): CEA levels over 5 ng/dl in ascites fluid are
associated with malignancy (J Clin Pathol 2001;54:831); but fluid in cysts may be CEA+ even when benign (Mod
Path 1998;11:1171)
Hepatocellular
carcinoma:
canalicular pattern for polyclonal CEA has 50-90% sensitive for hepatocellular
carcinoma, >95% specific (Mod
Path 2002;15:1279); CEA-Gold is 76% sensitive (AJSP
2002;26:978);
monoclonal CEA is usually negative (Hum
Path 2002;33:1175)
Microvillous
inclusion disease of small intestine: cytoplasmic staining of surface enterocytes (AJSP
2002;26:902)
Pancreatic
adenocarcinoma: monoclonal
Micro
images: ampulla
of Vater-Paneth cell carcinoma (figure G);
breast
adenoid cystic carcinoma; cervical
adenocarcinoma-signet ring cell type (figure D); cervical
adenocarcinoma-intestinal differentiation (figure D); cervical
adenoid cystic carcinoma #1; #2;
colon
carcinoma #1; #2; colon
inverted hyperplastic polyp (normal colon at upper right is CEA neg); gastric adenocarcinoma
metastatic to colon; hepatocellular
carcinoma (polyclonal CEA); hepatocellular
carcinoma vs. cholangiocarcinoma (note different staining patterns); hepatocellular
carcinoma-clear cell variant (figure A);
liver-poorly
differentiated adenocarcinoma (figure 4D);
lung
adenocarcinoma metastatic to ovary (figure 2B); mediastinal
neuroendocrine carcinoma; medullary thyroid
carcinoma; ovarian
mucinous and colonic adenocarcinoma;
Paget’s
disease of vulva; Paget’s disease of
scrotum; peritoneal
benign multicystic mesothelioma (an atypical finding, figure 2F); secretory meningioma
#1; #2; sweat
gland carcinoma #1 (figure 8B); #2 (porocarcinoma); various
images-quality control
Cytology
images: adenocarcinoma
in pleural fluid; cholangiocarcinoma
Positive staining (normal): granulocytes and epithelial cells
(apical surfaces); also biliary tract including gallbladder, colon (fetal),
hepatocytes, prostatic secretory cells (25%), small intestinal crypts; small
intestinal goblet cell mucin (not intracytoplasmic), thyroid cell nests and C
cells
Positive staining (tumors): bile duct tumors (benign or
malignant), bladder adenocarcinoma and benign tumors, breast ductal and
secretory carcinoma, CASTLE (AJSP
2006;30:994),
cervical adenocarcinoma (Archives 2003;127:1586) and squamous cell carcinoma, cholangiocarcinoma (monoclonal and
polyclonal, cytoplasmic and luminal but not canalicular pattern), chordoma
(variable), choriocarcinoma of placenta and testes (25%,
AJCP
1986;86:538), clear cell papulosis of skin, colorectal carcinoma (almost all,
throughout cell surface), endometrial adenocarcinoma (50%, focal, AJSP
1982;6:151
but negative with monoclonal CEA, Mod
Path 2006;19:1091),
gallbladder
dysplasia/carcinoma (cytoplasmic and luminal staining), gastric adenocarcinoma,
hepatoblastoma (polyclonal antibody, canalicular pattern, particularly in fetal
subtype), hepatocellular carcinoma (polyclonal CEA, canalicular pattern, 90%, Hum
Path 2005;36:1226), hepatoid adenocarcinoma (AJSP
2003;27:1302),
lung
adenocarcinoma, lung squamous cell carcinoma (nonkeratinizing, 77%, Mod
Path 2006;19:417), neuroendocrine (including
carcinoid) tumors (variable), ovarian mucinous tumors including carcinoma (92%,
AJCP
2001;116:246),
Paget’s disease (breast, vulva, scrotum), pancreatic adenocarcinoma (including foamy gland
variant, AJSP
2000;24:493 and lining of cysts, Mod
Path 2005;18:1157), penile clear cell carcinoma (AJSP
2004;28:1513),
salivary gland tumors (various), secretory meningioma; sweat gland tumors including
carcinoma (73%, Archives 2001;125:498), synovial sarcoma (variable), thymoma, thyroid medullary carcinoma, urothelial
carcinoma
Negative staining: breast carcinoma (usually),
endometriosis, mesothelioma (including testis, AJSP
2006;30:1), ovarian endometrioid and serous
carcinoma (Archives 1999;123:909), prostate adenocarcinoma (AJCP
2002;117:471), renal cell carcinoma, thymic
carcinoma (usually), thyroid carcinoma other than medullary
CD66f
Also called pregnancy-specific
beta-1 glycoprotein, PSG1
May be involved in immune
regulation, protection of fetus from maternal immune system
Released into maternal circulation
during pregnancy
Low levels in maternal blood predict
spontaneous abortion
Uses: no significant clinical use by
pathologists
Micro images: various
images (pages 20-22)
Positive staining (normal): syncytiotrophoblasts, fetal liver,
myeloid cells
Positive staining (disease): hydatidiform and invasive moles,
choriocarcinoma (J Clin Pathol 1977;30:19)
References: OMIM
176390
Deleted; now CD66b
Also called KP1, macrosialin
May have role in macrophage
phagocytic activities
Specific to lysosomes, not cell
lineage; epithelial cells activated by E coli may be
CD68+ (Toxicol
In Vitro 2002;16:405)
Binds to tissue and organ specific
lectins or selectins, allowing homing of macrophage subsets to particular sites
Uses: marker of histiocytes and histiocytic tumors;
presence in postportoenterostomy liver biopsies for extrahepatic biliary
atresia is associated with favorable prognosis (J
Pediatr Surg 2005;40:1252)
Micro images: acute demyelinating
disease; AML-M4; AML-M5; atypical
epithelioid angiomyolipoma of kidney;
breast
carcinoma-treatment effect (figure C);
cholesterol
granuloma of temporal bone; Castleman’s
disease; chronic
myelomonocytic leukemia with eosinophilia (figure C); Crohn’s
disease; crystal storing
histiocytosis within lymphoma; endometrial
nodular histiocytic hyperplasia (figure 3);
Erdheim-Chester
disease #1-lung (figure 5); #2-liver
(figure 5); follicular dendritic
cell tumor; gastrointestinal
stromal tumor with osteoclast-like giant cells (figure 3b); Gaucher’s disease
(presumptive) in spleen; giant
cell granuloma of temporal bone (figure C);
granular
cell tumor (figure 2B); histiocytic
sarcoma (figure 5); HIV associated
encephalopathy; inflammatory
demyelinating pseudotumor (brain); juvenile
xanthogranuloma-adult (figure 4); Kikuchi’s disease; Kikuchi-like
lymphadenopathy #1 in lupus; #2; #3; Kupffer
cells in alcoholic liver disease (figure 6); Langerhans
cell histiocytosis; leiomyosarcoma
with osteoclast-like giant cells (figure D); lymph
node-tingible body macrophages; multiple
sclerosis; myeloid
sarcoma #1 (figure 1d); #2-spine; #3-uterus; nerve-Wallerian
degeneration; plexiform
fibrohistiocytic tumor #1 (figure 3);
plasmacytoid
monocyte tumor; Rosai-Dorfman
disease #1-figure D; splenic
hamartoma (figure 3B); thyroid
gland giant cell granuloma (figure C);
viral
myocarditis; xanthogranulomatous
pyelonephritis (figure 4); quality control
Micro images (Mod Path subscribers): Kupffer
cells in normal liver; Kupffer
cells in severe non-alcoholic steatohepatitis (figure B)
Positive staining (normal): macrophage/monocytes (including
Kupffer cells and microglia), basophils, dendritic cells, fibroblasts (Verh
Dtsch Ges Pathol 2003;87:215, Ann Rheum Dis 2004;63:774), Langerhans cells, mast cells, myeloid cells, CD34+
progenitor cells, neutrophils, osteoclasts, activated platelets, B and T cells;
fetal small intestinal inclusions (Cesk
Patol 2001;37:7)
Positive staining (tumors): AML-M4/M5, angiosarcoma, atypical
fibroxanthoma, B cell lymphoma (some), blastic NK lymphoma, calcifying
aponeurotic fibroma (Hum
Path 1998;29:1504),
cellular fibrous histiocytoma (83%, J
Cutan Pathol 2006;33:353), chronic intervillositis (Hum
Path 2000;31:1389),
dermal dendrocytoma, dermatofibroma (42%, J
Cutan Pathol 2006;33:353), Erdheim-Chester disease (AJSP
1999;23:17),
follicular dendritic cell tumor (AJSP
1998;22:1048),
Gaucher
cells (AJCP
2004;122:359), giant cell angioblastoma, giant
cell tumors (extrahepatic biliary tree- AJSP
2006;30:495;
soft tissue-AJSP
2000;24:386,
synovial type-Hum
Path 2003;34:670),
granular
cell astrocytoma (AJCP
2006;126:602), granular cell tumor (Archives 2004;128:771), granulocytic (myeloid) sarcoma
(AJSP
1997;21:1156), hairy cell leukemia, hereditary
disorders (ceruloplasmin deficiency-macrophages in striatum
#1; #2),
histiocytic sarcoma (AJSP
2001;25:1372), HIV encephalopathy (Am J Pathol 2004;164:2089), inflammatory myofibroblastic
tumor/pseudotumor (AJCP
2003;120:56),
interdigitating
dendritic cell sarcoma (AJSP
2002;26:530, AJCP
2001;115:589), juvenile xanthogranuloma (AJSP
2003;27:579),
Kikuchi’s disease (AJSP
1999;23:1040), Langerhans cell histiocytosis
(usually, Blood 2001;97:1241), malignant fibrous histiocytoma, mastocytosis and
mast cell disease (AJSP
2000;24:703), melanoma (Mod
Path 1999;12:1072), mycobacterial pseudotumor (AJSP
1999;23:656),
myelodysplasia
bone marrow nodules (AJCP
2003;120:874),
neuroma, nodular fasciitis, osteoclast-like giant cells in tumors of pancreas
and urinary tract (Archives
1998;122:266, Mod
Path 2006;19:161),
pigmented villonodular synovitis (Hum
Path 2003;34:65),
pleomorphic xanthoastrocytoma, plexiform xanthomatous tumor (AJSP
2002;26:1302),
primitive non-neural granular cell tumor of skin (AJSP
2005;29:927),
renal
cell carcinoma (AJCP
1995;103:425), reticulohistiocytoma (AJSP
2006;30:521),
Rosai-Dorfman disease (Mod
Path 2001;14:172),
schwannoma,
signet ring-like cells (benign, AJCP
2001;115:249),
splenic diffuse hemangioma (AJSP
1997;21:827),
splenic littoral cell angioma (AJSP
2006;30:1036),
steatohepatitis
(Mod
Path 2002;15:699), Whipple’s disease, xanthelasma (Archives 2003;127:e417), xanthogranulomatous pyelonephritis (Archives 2005;129:e209), xanthoma (Hum
Path 2003;34:814)
Negative staining: atypical fibrous histiocytoma (AJSP
2002;26:35),
megakaryocytes
References: OMIM 153634, AJCP
2004;122:794 (comparison with CD163)
Also called activation inducer
molecule (AIM), early activation antigen (EA-1)
Earliest inducible cell surface
glycoprotein acquired during lymphoid activation
Involved in early events of T cell,
NK cell, monocyte and platelet activation
Associated with Th-1 T cell
differentiation and associated cytokines (IL-2, TNF-alpha, interferon-gamma, Hum
Path 2002;33:330)
Highly expressed on T cells from
inflammatory infiltrates of rheumatoid arthritis (Clin
Exp Rheumatol 2004;22:331), viral hepatitis, autoimmune thyroid disorders
Expression on CD3+ and CD8+
peripheral blood T cells correlates with acute graft rejection in renal
allograft recipients (Transplantation
2003;76:190)
May promote lymphocyte retention in lymphoid organs (Nature
2006;440:540)
Uses: no significant clinical use by
pathologists
Positive staining (normal): activated T cells, B cells, NK
cells, neutrophils, eosinophils, epidermal Langerhans cells, platelets,
thymocytes
Positive staining (disease): peripheral T cell lymphoma (AJCP
2003;120:866)
References: OMIM 107273
Also called CD27 ligand
Cytokine that belongs to tumor
necrosis factor ligand family
Has role in T cell activation (J Immunol 2006;176:7726)
Induces T cell proliferation and
enhances generation of cytolytic T cells (Clin
Exp Immunol 2002;130:424)
Escape of immune surveillance occurs
by inducing apoptosis in CD27+ B and T cells in glioma (Cancer Res 2002;62:2592) and renal cell carcinoma (Neoplasia 2006;8:933); also infection by chronic lymphocyte
choriomeningitis virus (J
Exp Med 2006;203:2405)
Uses: possibly to differentiate thymic carcinoma (CD70+)
from thymoma (CD70-), or to identify clear cell variant of renal cell carcinoma
(CD70+)
Micro images: various images
Positive staining (normal): activated B and T cells, monocyte
derived dendritic cells (J Leukoc Biol 2004;76:1134)
Positive staining (disease): ALL (Exp
Hematol 2005;33:1500), CLL (Blood 1995;85:3556), Hodgkin’s lymphoma (Reed-Sternberg cells), glioma,
medulloblastoma, nasopharyngeal carcinoma (Am
J Pathol 1995;147:1152), renal cell carcinoma (clear cell type, J
Urol 2005;173:2150), thymic carcinoma (AJSP
2000;24:742)
Negative staining: thymoma (most)
References: OMIM 602840
Also known as transferrin receptor
Present on actively proliferating
cells; essential for iron transport into proliferating cells (benign and
malignant)
Iron bound apotransferrin binds
CD71, is internalized to endosome, which becomes acidic; the acidic pH leads to
iron release, iron-free apotransferrin is returned to cell surface; surface pH
causes iron-free apotransferrin to lose affinity for CD71, is released into
circulation, allowing a new cycle to begin
Drawing: transferrin-iron
cycle
Major IgA receptor on mesangial
cells (J Am Soc Nephrol 2003;14:327)
Uses:
high serum levels can diagnose hemolytic anemia (Ann
Hematol 2003;82:228) or other anemic conditions; similar to TIBC for
differentiating iron deficiency anemia from anemia of chronic disease (AJCP
2001;115:112);
not useful for detection of early iron deficiency (Ann
Clin Lab Sci 2005;35:435); used to detect micronucleated reticulocytes / Howell-Jolly bodies by
flow cytometry (Mutat
Res 2003;542:77),
also used to test for erythropoietin doping by athletes
Micro images: normal and diseased
kidney
Positive staining (normal): all proliferating cells; erythroid
precursors through reticulocytes, capillary endothelium in brain
Positive staining (disease): AML M6, anaplastic large cell
lymphoma (AJSP
1988;12:264),
primary
effusion lymphoma (AJCP
1996;105:221);
other tumors
References: OMIM
190010
Cell surface protein expressed exclusively
on B cells
Regulates mature B cell
differentiation, prevents differentiation of naive B cells into plasma cells (Eur
J Immunol 2005;35:2325)
Ligand of CD5 (J
Immunol 1992;148:1630) and CD100 (Int Immunol 2005;17:1277)
Not the same as DBA.44 (abstract in AJSP
1996;20:613 is apparently wrong)
Increased nucleotide mutation of
CD72 mRNA accounts for decreased CD72 expression in B cells of teenage SLE
patients (Pediatr
Allergy Immunol 2006;17:565)
Uses:
marker of B cells (not commonly used)
Positive staining (normal): B cells only
Positive staining (disease): B cell lymphoma
Negative staining: plasma cells (Am
J Hematol 1992;41:151)
References: OMIM 107272
Also called ecto-5'-nucleotidase
Catalyzes dephosphorylation of ribo-
and deoxyribonucleotides to their corresponding nucleosides, such as 5’ AMP to
adenosine
Mediates costimulatory signals in T
cell activation
Mediates lymphocyte adhesion to
dendritic cells (Blood 1996;88:1755) and endothelium (J Immunol 2000;165:5411)
May protect against vascular
inflammation and neointima formation (Circulation
2006;113:2120)
May be a lymphocyte maturation
marker
Uses: no significant clinical use by
pathologists
Positive staining (normal): B and T cell subset, endothelial
cells, follicular dendritic cells, epithelial cells
References: OMIM 29190
Also called LN2, HLA-DR-associated
invariant chain
Gamma chain antigen associated with
MHC class II antigen and antigen presentation
MHC class II chaperone-stabilizes
alpha/beta heterodimers in a complex soon after synthesis, and directs
transport of the complex from the endoplasmic reticulum to compartments where
peptide loading of class II takes place
H. pylori urease binds to CD74 on gastric epithelial cells (Infect Immun 2006;74:1148), and
upregulates CD74 expression (J Immunol 2005;175:171)
Has important role in mucosal
immunity
Receptor for macrophage migration
inhibitory factor, a proinflammatory cytokine (J
Immunol 2006;177:8730)
Associated with perineural invasion in pancreatic
carcinoma (Clin
Cancer Res 2006;12:2419)
Uses: B cell marker (not commonly used)
Micro images: normal tonsil; increased expression
in H. pylori+ epithelium #1; #2; multiple
myelomas (figures G-J); renal tumors
(figures D-F)
Positive staining (normal): B-cells, activated T-cells,
macrophages, interdigitating dendritic cells, activated endothelial and
epithelial cells
Positive staining (disease): many B cell lymphomas, myeloma (Clin Cancer Res 2004;10:6606), some T cell lymphomas,
Reed-Sternberg cells, many myeloid leukemias, Langerhans cell histiocytosis;
renal clear cell and chromophobe carcinoma (most, Am J Pathol 2001;158:1639)
Negative staining: renal oncocytoma
References: OMIM 142790
Also called lactosamines, LN-1;
formerly CDw75
A carbohydrate, not a protein (Cell
1992;68:1003)
Ligand for CD22 (Cell
1991;66:1133)
A neuraminidase-sensitive lymphocyte
cell surface differentiation antigen
Strong expression associated with
better prognosis in follicular center cell lymphoma (J
Pathol 2006;209:352)
Uses:
marker of follicular center cell lymphoma; identify Reed-Sternberg cells (not
commonly used)
Micro images: lymphocyte
predominance Hodgkin’s lymphoma; marginal
zone lymphoma (aberrant expression)-figure 4
Positive staining (normal): mature B cells (germinal center
derivation), erythrocytes, some T cells, some epithelial cells,
Positive staining (disease): “popcorn cells” of lymphocyte
predominance Hodgkin’s lymphoma, many B cell lymphomas (Histopathology
1999;35:209)
References: Archives 2002;126:862
CD75s
Alpha-2,6-sialylated lactosamines
(formerly CDw76)
A carbohydrate, not a protein
Marker of murine CD8+ suppressor T
cells (Int
Immunol 2003;15:1389)
Uses: no significant clinical use by
pathologists
Positive staining: B cells, some T cells
Renamed CD75s at 7th HLDA Workshop
Also called globotriaosylceramide
pK blood group antigen on
erythrocytes
A carbohydrate, not a protein
Endothelial receptor for verotoxins
(J
Biol Chem 2006;281:10230), including from Shigella dysenteriae
and E. coli
Also interacts with CD19 (J
Cell Physiol 1998;176:281)
Mediates apoptosis of
renal vascular endothelial cells and intestinal epithelial cells,
resulting in hemolytic uremic syndrome
Does NOT discriminate centroblasts
from centrocytes
Also expressed by liver flukes (Biol
Chem 2001;382:195)
Uses: identify germinal center cells
Positive staining (normal): B cells (centrocytes, centroblasts,
plasmablasts, J
Immunol 2006;177:4341), megakaryoblasts and platelets (J Biol Chem 2002;277:11247)
Positive staining (disease): Burkitt's lymphoma
References: OMIM 607922
(CD77 synthase)
Deleted at 7th HLDA Workshop
(reasons unknown)
Defines a conformation of MHC class
II molecules bound to peptides acquired through trafficking to lysosomal
antigen processing compartments, and not MHC class II molecules associated with
tetraspanins (J
Immunol 2006;177:5451)
Appears on B cells following HLA-DR
and preceding CD10, CD19, CD22 and CD37
Uses: no significant clinical use by
pathologists
Positive staining (normal): B cells
Also called MB-1, B-cell antigen
receptor complex associated protein alpha-chain
Encodes Ig-alpha protein of the
B-cell antigen receptor; the receptor also includes Ig-beta protein (CD79b) and
surface immunoglobulin
Expressed early in B-cell
differentiation (often positive when mature B-cell markers are negative); also
expressed in plasma cells
In AML, presence usually represents
aberrant B cell antigen in leukemias of distinct myeloid linage, not
biphenotypic differentiation (Cancer
Genet Cytogenet 2005;163:62)
CLL patients have low B cell-IgM surface expression
due to defects
in glycosylation and folding in µ and CD79a chains (Blood 2005;105:2933)
Less specific than PAX5 for acute leukemia (Cancer Res 2004;64:7399)
Uses: general detection of B cells/B cell origin (with
CD20); also
- in ALL or small B cell lymphoproliferative disorders
when CD20 may be negative (AJCP
2006;126:534)
or after rituximab (anti CD-20) therapy (AJSP
2005;29:1399)
- in infarcted lymphomas (Archives 2003;127:60)
- to differentiate preB
lymphoblastic lymphoma from
Micro images: measles
related appendicitis: Warthin-Finkeldey giant cells (figure C); prominent
CD79+ hematogones in fatal Shwachman-Diamond syndrome (figure 2C); follicular dendritic
cell tumor; lymphoid infiltrate in ileal
ulcer; lymphoplasmacyte
rich meningioma; quality
control
leukemia/lymphoma - infarcted
lymphomas (figures 2 & 6); primary mediastinal
B cell lymphoma; pro B
acute lymphoid leukemia (bottom left);
peripheral
T cell lymphomas #1; #2
(figure 2B); T cell
lymphoblastic leukemia (middle right);
t(8;21)
myeloid leukemia (bottom right); T
cell lymphoblastic lymphoma with coexisting Langerhans cell histiocytosis
(figure B)
Positive staining (normal): B cells, plasma cells
Positive staining (disease): B cell leukemia / lymphoma (but
variable staining in plasmablastic lymphoma and primary effusion lymphoma);
nodular lymphocyte predominant Hodgkin’s lymphoma (faint, AJCP
2003;119:192),
classic Hodgkin’s lymphoma (18%, Mod
Path 2004;17:1531), t(8,21) myeloid leukemias, T cell
leukemias/lymphomas (some, AJCP
2000;113:823), primary plasmacytoma of lymph node (Hum
Path 1997;28:1083)
Negative staining: anaplastic large cell lymphoma (Hum
Path 2004;35:455),
granulocytic sarcoma
References: OMIM 112205, Blood 1995;86:1453 (early study)
CD79b
Also called B29, B-cell antigen
receptor complex associated protein beta-chain
Encodes the Ig-beta protein of the
B-cell antigen receptor; the receptor also includes Ig-alpha protein (CD79a)
and surface immunoglobulin
First expressed in cells
with Ig µ chains and remains expressed throughout B cell
differentiation to plasma cells
Uses: distinguish CLL from other B cell disorders if
intensity of staining is considered (J Clin Pathol 2002;55:180)
Flow cytometry images: CLL
Micro images: normal tonsil
Positive staining (normal): B cells, plasma cells
Positive staining (disease): B cell lymphoma and
lymphoproliferative disorders - CLL (18%, Archives 2003;127:561), CLL with IgM paraproteins (58%, AJCP
2005;123:594), lymphoplasmacytic
lymphoma (85%, AJCP
2005;124:414)
Negative staining: hairy cell leukemia (usually)
References: OMIM
147245
Also called B7-1, BB1
T cells need two signals for
activation; the first signal is antigen peptide presented on MHC class II
through the T cell receptor
The second (costimulatory) signal
is delivered by CD80 or CD86, expressed on surface of antigen
presenting cells, which interact with either CD28 or CD152 (CTLA-4)
Has critical role in autoimmune,
humoral, and transplant responses
Increased expression may
cause excessive antigen presentation in fulminant hepatic failure as
an early step in its pathogenesis before the onset of tissue damage
(Am J Pathol 1999;154:1711)
Receptor for some adenovirus species
(Virus
Res 2006;122:144)
Uses: no significant clinical use by
pathologists
Diagram: CD80/86
binding and antagonism by drug abatacept
Micro images: normal esophagus; esophageal carcinoma; inflamed skin
Positive staining (normal): activated B cells, T cells,
macrophages, dendritic cells
References: OMIM 112203
Also called Target of an
Anti-Proliferative Antibody (TAPA1)
Receptor for Hepatitis C Virus E2
protein in B cells (J
Virol 2006;80:8695)
Also required for Plasmodium falciparum infectivity (Nat
Med 2003;9:93)
Upregulation on HIV1+ B cells may ultimately cause
lymphoproliferative disorders (Clin
Exp Immunol 2007;147:53)
On B cells, is complexed with CD21, CD19 and Leu13;
facilitates complement recognition
Member of tetraspanin family; has
close associations with major histocompatibility complex class I/II proteins
Appears to promote muscle cell
fusion and support myotube maintenance
Uses: no significant clinical use by
pathologists
Positive staining (normal): lymphocytes, endothelial cells,
epithelial cells
Positive staining (tumor): HCV+ splenic diffuse large B cell
lymphoma (Hum
Path 2005;36:878); Burkitt’s lymphoma cell lines, neuroblastoma cell lines (J
Pediatr Hematol Oncol 2000;22:20)
Negative staining: erythrocytes, platelets,
neutrophils
References: OMIM 186845
Also called prostate cancer
antimetastasis gene KAI1, kangai 1 (Chinese for anticancer).
Metastasis suppressor gene
Expression correlates with p53
expression
Reduced expression of CD82 is
associated with metastases/poor prognosis in carcinomas of bladder (Int
J Urol 2004;11:74), breast (Am J Pathol 1998;153:973,
J
Cancer Res Clin Oncol 2005;131:191), colon (World J Gastroenterol 2004;10:2245), endometrium (Clin Cancer Res 2003;9:1393), larynx (Lin
Chuang Er Bi Yan Hou Ke Za Zhi 2005;19:1065), oral cavity (Clin Cancer Res 2002;8:828), thyroid (Int
J Mol Med 2004;14:517, Pathol
Res Pract 2003;199:79)
Expression reduces function of
urokinase-type plasminogen activator receptor (J Biol Chem 2005;280:14811)
Uses:
possible use as prognostic marker (see above)
Micro images: breast carcinoma; colon carcinoma: membranous
and cytoplasmic staining #1-HT29 cell lines; #2-SW480 cell lines; #3-colon carcinoma
cells; endometrial
carcinoma; oral
cavity (normal and malignant); prostatic adenocarcinoma
#1-well differentiated; #2-poorly differentiated
Positive staining (normal): activated/differentiated
hematopoietic cells, endothelial cells, epithelium
Negative staining: erythrocytes
References: OMIM 600623
Also called HB15
May assist in antigen presentation
or cellular interactions that follow lymphocyte activation.
Soluble form inhibits dendritic cell
maturation and inhibits dendritic cell-mediated T cell proliferation (J
Med Dent Sci 2006;53:85)
Elevated serum levels seen in mantle
cell lymphoma and CLL (Leuk
Res 2004;28:237)
Higher number of activated dendritic cells may be good prognostic factor for breast carcinoma (Int J Cancer 2003;104:92), cholangiocarcinoma (Hum Path 2004;35:881), colorectal liver metastases (Hum Path 2004;35:1392), gallbladder carcinoma (