CD Markers
CD44

Author: Nat Pernick, M.D. (see Authors page)

Revised: 31 December 2015, last major update October 2013

Copyright: (c) 2003-2015, PathologyOutlines.com, Inc.

PubMed Search: CD44[title]

Related topics: CD44R
General
  • Cell membrane glycoprotein involved in cell-cell interactions, cell adhesion and migration
  • Also called CD44s (standard isoform) or CD44H, which lacks all alternative exons; all references below are to standard isoform unless stated otherwise
  • Also known as phagocytic glycoprotein 1
  • CD44 splicing variants may mediate invasion of trophoblast into maternal tissue in early pregnancy (Eur J Obstet Gynecol Reprod Biol 2006;128:243)
  • May help lymphomas disseminate by binding to high endothelial venules
  • May be an activity marker in multiple sclerosis (J Neuroimmunol 2005;166:189)
  • CD44 splice variants are assumed to have a critical role in the malignant progression of many human tumors, but the clinical significance of CD44 expression is not yet understood
  • Enhanced cell surface CD44v6 and v9 expression by osteopontin in breast cancer epithelial cells facilitates tumor cell migration (Clin Exp Metastasis 2005;22:663)
  • The Indian blood group (OMIM #609027) has antigens In(a) and In(b), which reside on CD44
  • Cardiovascular disease: CD44 may induce monocytes to become foamy macrophages and cause atherosclerotic lesions (Biochem Biophys Res Commun 2006;339:846); there is increased expression of CD44 and variants in atheroma and abdominal aortic aneurysm (Am J Pathol 2004;165:1571); high levels on monocytes are associated with coronary arteriogenesis and development of collateral vessels (Circulation 2004;109:1647); closure of ductus arteriosis with wall remodeling involves CD44v6+ smooth muscle cells versus CD44v6 neg smooth muscle cells in patent or closed ductus arteriosis (Am J Cardiol 2006;97:1056)
  • References: OMIM #107269
Pathophysiology
  • Family of cell surface glycoproteins with numerous isoforms and posttranslational modifications involving glycosylation (CD44v6 is common variant) generated by alternate splicing of mRNA
  • Important in epithelial cell adhesion (cell-cell and cell-matrix) to hyaluronate in basement membranes, and maintaining polar orientation of cells; this process may contribute to tissue remodeling and may stimulate cell proliferation and migration
  • CD44 also binds hyaluronic acid, laminin, collagen, fibronectin, osteopontin, matrix metalloproteinases and E-selectin / CD62E (J Exp Med 2005;201:1183)
  • Also considered a marker of activated B cells
  • Important in development of T cells; double negative (CD4-, CD8-) immature thymocytes are divided into developmental stages based on the expression of CD44 and CD25 (Immunol Res 2010;47:45)
  • Involved in leukocyte attachment and rolling on endothelial cells, homing to peripheral lymphoid organs (by binding to mucosal addressin, a protein present on high endothelial cells of Peyer’s patches and lymph nodes), and leukocyte chemotaxis and aggregation
Uses by Pathologists
  • Marker of squamous epithelium
  • Expression in flow cytometry may differentiate Burkitt's lymphoma (low) from CD10+ diffuse large B cell lymphoma (Am J Clin Pathol 2010;133:718)
  • May help differentiate reactive urothelium (diffuse full thickness staining) from carcinoma in situ (variable basal cell membranous staining, Am J Surg Pathol 2001;25:1074)
Prognostic Factors
  • In general, loss of CD44 expression is a poor prognostic factor, and expression of particular variants may be a poor prognostic factor for particular diseases
  • Breast carcinoma: CD44v7-v8 expression is associated with poor long term prognosis (J Exp Clin Cancer Res 2005;24:75), but CD44s expression is associated with increased disease free survival in node negative patients (Clin Cancer Res 2005;11:3309)
  • Carcinoid tumors: loss of CD44s is associated with nodal metastases (Mod Pathol 2002;15:1333)
  • Colon carcinoma: high levels of CD44s are associated with responding to treatment (Oncol Rep 2004;11:41)
  • Gastrointestinal stromal tumor: in gastric tumors, loss of CD44s is associated with poor clinical outcome (Am J Surg Pathol 2004;28:168)
  • Laryngeal carcinoma: reduced expression of CD44 is a poor prognostic factor (Anticancer Res 2005;25:1115)
  • Lung carcinoma: reduced CD44v3 expression is associated with poor prognosis in non-small cell lung cancer (Hum Pathol 2000;31:1088)
  • Lymphoma: high serum soluble CD44 levels are associated with poor prognosis in non-Hodgkin’s lymphoma (Leuk Res 2002;26:241)
  • Melanoma: reduced cell surface CD44 is associated with poor prognosis (Am J Pathol 2000;157:957)
  • Myeloma: presence of CD44v9 is associated with poor prognosis
  • Neuroblastoma: CD44 is powerful predictive factor for outcome at initial staging - increased levels are associated with better prognosis (J Clin Oncol 1996;14:25, Eur J Cancer 1997;33:2101)
  • Ovarian carcinoma: high CD44 expression is associated with favorable outcome (Clin Cancer Res 2003;9:5318)
  • Pheochromocytoma: loss of CD44S is associated with metastases (Mod Pathol 2004;17:1119)
  • Prostate cancer: loss of CD44 is associated with poor outcome
  • Thymoma: increased CD44v5 expression is associated with poorer survival (Ann Thorac Surg 2003;76:213)
  • Tongue carcinoma: reduced expression is a poor prognostic factor (Anticancer Res 2003;23:5197)
  • Urothelial neoplasms, papillary: loss of CD44 immunoreactivity (restricted to basal cell layer in normal urothelium) is associated with increasing tumor grade and stage in pTa and pT1 patients (Mod Pathol 2000;13:1315)
Micro Images

Images hosted on other servers:

Cutaneous melanoma
(fig B, D)

Ovarian carcinoma

Atheroma and abdominal aortic aneursym


Left: adenosquamous carcinoma; right: breast carcinoma

Left: sclerosing hemangioma of lung (fig D); right: squamous cell carcinoma (various)



Images hosted on Nature.com:
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Pheochromocytoma (fig D,E)


Bladder and CD44-
Missing Image

Normal urothelium
(fig 1A)

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Papilloma
(fig 2B)

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Papillary urothelial neoplasm of
low malignant potential (fig 3B)


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Papillary carcinoma-low grade (fig 4B)

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Papillary carcinoma-high grade (fig 5B)

Positive Staining - Normal
  • Most tissues are CD44+; including astrocyte restricted precursor cells (Dev Biol 2004;276:31), breast myoepithelial cells (CD44v6), colon, lung type II pneumocytes, red blood cells, stomach, urothelial basal cells, uterus and white blood cells
Positive Staining - Disease
Negative Staining