CD 56 (Neural Cell Adhesion Molecule)

Dako (MOC-1, T199), Monosan (123C3), Research Diagnostics (ERIC-1) and Zymed (123C3).

Applicable to formalin-fixed paraffin sections. Requires pretreatment with microwave or pressure cooker antigen/epitope retrieval in citrate buffer. Enzymatic pretreatment has been shown to markedly decrease reactivity. The antibody to CD 56 may also be applied to frozen sections or cell smears.

CD 56, the neural cell adhesion molecule (NCAM), was discovered in a search for cell surface molecules that contribute to cell-cell interactions during neural development (Rutishauer et al, 1988). Human peripheral cells capable of non-MHC restricted cytotoxicity express the CD 56 antigen. NCAM has at least three isoforms, generated by differential splicing of the RNA transcript from a single gene located on chromosome 11 (Cunningham et al, 1987). The core polypeptide of the CD 56 appears to be the 140 kD isoform of NCAM, which is variably glycosylated and sialylated to produce mature species with molecular weights ranging from 175 to 220 kD. The CD 56 antigen itself appears not to participate directly in the cytolytic activity of NK cells (Ritz et al, 1988). Subsequent immunohistochemical studies have shown that NCAM is widely expressed in neural and neuroendocrine tissues (Bourne et al, 1991). Antibody clone 123C3 recognizes a heterodimeric glycoprotein with the 145 and 185 kD isoforms of NCAM (Schol et al, 1988), whilst clone ERIC-1 has been reported with two human isoforms, 145 and 180 kD, of NCAM. T199 is a 135-220 kD single-chain glycosylated and sialylated protein expressed on CD 2+, CD 3-, CD 16+ natural killer cells (NK) and neuroectodermal cells (Feidkert et al, 1989). Autopsy tissue has been used to demonstrate strong CD 56 immunoreaction in peripheral nerve, adrenal zona glomerulosa and medulla and synapses in cerebral cortex. CD 56 also marks thyroid follicular epithelium, proximal renal tubules, hepatocytes, gastric parietal cells and pancreatic islet cells (Shipley et al, 1997).

Merkel cell carcinoma, neuroblastoma, ganglioglioma, oligodendroglioma, glioblastoma multiforme, pheochromocytoma, retinoblastoma, laryngeal and pulmonary squamous cell carcinoma, pulmonary and intestinal carcinoid, pulmonary small cell undifferentiated carcinoma, pancreatic islet cell tumor, hepatocellular carcinoma, renal cell carcinoma and follicular and papillary thyroid carcinoma mark positively with CD 56 antibodies. CD 56 has been found to be negative in Ewing sarcoma, nasopharyngeal carcinoma, colonic adenocarcinoma, melanoma, meningioma, follicular center cell lymphoma, hairy cell leukemia (one case each respectively) and multiple myeloma (five cases). However, the current major application of CD 56 on paraffin sections is in the diagnosis of NK and NK-like T-cell lymphoma, i.e. CD 56 being a marker for natural killer cells (Chan, 1997). CD 56+ lymphomas are heterogeneous, encompassing several entities: nasal/nasopharyngeal NK/T-cell lymphoma, nasal-type (extranasal) NK/T-cell lymphoma, aggressive NK-cell leukemia/lymphoma and the newly described blastoid NK-cell lymphoma. The nasal form represents the prototype of this group and is referred to as angiocentric lymphoma in the REAL classification. Since CD 56+ lymphomas do not always show angiocentricity, and angiocentricity may occur in other lymphoma types, the term NK/T-cell lymphoma or T/NK-cell lymphoma appears to be more appropriate. Two other types of T-cell lymphoma show a particularly high frequency of CD 56 expression: hepatosplenicdgT-cell lymphoma (63% CD 56+) and S-100 protein-positive T-cell lymphoma (Chan et al 1987; Wong et al, 1995).

Clearly CD 56 antibodies are essential for the diagnosis of NK/T-cell lymphomas which show a predilection for the upper aerodigestive tract, skin, testes, skeletal muscle, gastrointestinal tract and other extranodal sites and pursue an aggressive clinical course. Furthermore, this antibody may be used to detect residual disease in CD 56+ NK/T-cell lymphoma in which the neoplastic lymphoid cells are small and show minimal atypia, especially in small biopsies.

•Bourne SP, Patel K, Walsh F et al 1991. A monoclonal antibody (ERIC-1), raised against retinoblastoma, that recognizes the neural cell adhesion molecule (NCAM) expressed on brain and tumors arising from the neuroectoderm. Journal of Neurological Oncology 10: 111-119.

•Chan JKC 1997. CD 56-positive putative natural killer (NK) cell lymphomas: nasal, nasal-type, blastoid, and leukemic forms. Advances in Anatomical Pathology 4:163-172.

•Chan JKC, Ng CS, Chu YC, Wong KF 1987. S-100 protein positive sinusoidal large cell lymphoma. Human Pathology 18:756-759.

•Cunningham BA, Hemperly JJ, Murray BA, Prediger EA, Brackenbury R, Edelman GM 1987. Neural cell adhesion molecule: structure, immunoglobulin-like domains, cell surface modulation, and alternative RNA splicing. Science 236:799-806.

•Feidkert HJ, Pietsch T, Hadam MR, Mildenberger H, Riehm H 1989. Monoclonal antibody T-199 directed against human medulloblastoma: characterization of a new antigenic system expressed on neuroectodermal tumors and natural killer cells. Cancer Research 49: 4338-343.

•Ritz J, Schmidt RE, Michon J, Hercend T, Schlossman SF 1988. Characterization of functional structures on human natural killer cells. Advances in Immunology 42: 181-211.

•Rutishauer U, Acheson A, Hall AK, Mann DM, Sunshine J 1988. The neural cell adhesion molecule (NCAM) as a regulator of cell-cell interactions. Science 240:53-57.

•Schol DJ, Mooi WJ, Van Der Gugten AA et al 1988. Monoclonal antibody 123C3, identifying small cell carcinoma phenotype in lung tumors, recognizes mainly, but not exclusively, endocrine and neuron-supporting normal tissues. International Journal of Cancer 2 (suppl): 34-40.

•Shipley WR, Hammer RD, Lennington WJ, Macon WR 1997. Paraffin immunohistochemical detection of CD 56, a useful marker for neural cell adhesion molecule (NCAM), in normal and neoplastic fixed tissues. Applied Immunohistochemistry 5:87-93.

•Wong KF, Chan JKC, Matutes E et al 1995. Hepatosplenic Tgd T-cell lymphoma: a distinctive aggressive lymphoma type. American Journal of Surgical Pathology 19: 718-726.

Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.