NCAM1

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Definition: NCAM1 (CD56) is a membrane-bound glycoprotein that plays a role in cell-cell and cell-matrix adhesion through both its homophilic and heterophilic binding activity. NCAM1 shares many features with immunoglobulins and is considered a member of the immunoglobulin superfamily.

Expression

The neural cell adhesion molecule NCAM1 appears on early embryonic cells and is important in the formation of cell collectives and their boundaries at sites of morphogenesis. Later in development it is found on various differentiated tissues and is a major CAM mediating adhesion among neurons and between neurons and muscle.

Function

 in nerves, NCMA1 regulates homophilic (like-like) interactions between neurons and between neurons and muscle; it 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.

 in hematopoiesis: CD56 is the prototypic marker of NK cells, also present on subset of CD4+ and CD8+ T cells.

 in cell adhesion: CD56 contributes to cell-cell or cell-matrix adhesion during development.

Ig superfamily

Ig superfamily members are known to mediate cell adhesion, as:
 NCAM1 (MIM.116930)
 ICAM1 (MIM.147840)
 VCAM1 (vascular cell adhesion molecule-1) (MIM.192225)

They also mediate antigen recognition:
 immunoglobulins (IGH, IGL, IGK)
 T-cell receptors (TCRA, TCRB, TCRD, TCRG)
 MHC molecules.

In addition, a subgroup comprising 30 members characterized by the presence of one or more immunoreceptor tyrosine-based inhibitory motifs (ITIMs) within their cytoplasmic domain has also been recognized. PECAM1, which has 6 ITIMs within its cytoplasmic domain, is a member of this subfamily;

Another subfamily is the carcinoembryonic antigen gene family (CEA gene family).

Functions

 N-CAM (NCAM1 or CD56) regulates homophilic (like-like) interactions between neurons and between neurons and muscle.

 CD56 also associates with fibroblast growth factor receptor (FGFR) 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.

 CD56 contributes to cell-cell or cell-matrix adhesion during development

 Lymphocyte activated killer phenomenon mediated by IL-2 activated CD56+, CD3-, NK cells

Expression in normal cells

 NK cells (80-90%)
 activated T cells
 cerebellum and brain at neuromuscular junctions
 normal neuroendocrine tissues
 bile ducts and biliary ductules (14576479)

Expression in tumors

 NK proliferations

• NK/T cell lymphomas
• blastic NK lymphoma
• blastoid NK lymphoma

 CD56+ intestinal T cell lymphoma / NK-like T cell lymphoma of ileum (large granular lymphocytes)

 myeloma
 myeloid leukemias
 rare CD56+ CD57+ B-ALL (15626024)

• B-ALL and CD56 and CD57 co-expression (Pediatr Hematol Oncol 2004;21:677)

 rare CD56+ plasma cell leukemia

• UPMC:470 Case

 cutaneous lymphoproliferative disorders with poor prognosis, other than cutaneous T cell lymphoma (J Clin Pathol 2007;60:981)

 neural or neuroendocrine differentiation

• adult neuroblastoma
• neuroendocrine tumors and neuroendocrine carcinomas (AJSP 2006;30:684)
• small cell lung carcinoma TTF1+, CD56+
• pheochromocytoma

 Wilms tumor
 pancreatic acinar cell carcinoma
 pancreatic endocrine neoplasm
 pancreatic solid-pseudopapillary tumor (Mod Path 2006;19:1409)
 Merkel cell carcinoma (J Dermatol Sci 2003;31:219)
 mesotheliomas (some)
 small cell carcinoma of cervix (Int J Gynecol Path 2005;24:113)
 sustentacular cell tumor (AJSP 2006;30:268)
 synovial sarcoma (usually, Mod Path 2006;19:659)
 thyroid carcinoma (AJCP 2003;120:64)

Negative expression of CD56

 granulocytes
 monocytes
 B cells
 ALL
 large granular NK cell lymphocytosis
 plasma cell leukemia
 pPNET/Ewing sarcoma

Prognostic use

 CD56 negative myeloma has poor prognosis.

 Predicts poor prognosis for cutaneous lymphoproliferative disorders other than cutaneous T cell lymphoma (J Clin Pathol 2007;60:981)

Diagnostic use

 Marker of NK cells and NK lymphomas

 myeloma

• Detect residual myeloma (Am J Clin Pathol 2009;132:60) and residual AML in bone marrow (Am J Clin Pathol 2008;129:934)
• Differentiate plasma cells in myeloma (CD56+) from reactive plasmacytosis or MGUS (CD56-, Am J Pathol 2002;160:1293, Am J Clin Pathol 2009;132:728)

 Detect neuroendocrine disorders (J Clin Pathol 2002;55:535)

• particularly if extensive crush artifact (J Clin Pathol 2005;58:978);
• other neuroendocrine markers are synaptophysin and chromogranin.

Differential diagnosis

 differentiates plasma cells in myeloma (CD56+) from reactive plasmacytosis or MGUS (CD56-, Am J Path 2002;160:1293)

References

 Matsubara K, Yura K, Hirata T, Nigami H, Harigaya H, Nozaki H, Fukaya T, Baba K. Acute lymphoblastic leukemia with coexpression of CD56 and CD57: case report. Pediatr Hematol Oncol. 2004 Oct-Nov;21(7):677-82. PMID: 15626024