CD56 (Neural cell adhesion molecules, NCAM, Leu19)

NCAM is a membrane glycoprotein homophilic cell adhesion molecule , originally isolated on the basis of its role in neural cell adhesion. There have been reports that NCAM positive carcinomas are more aggressive than NCAM negative carcinomas6.

Antibodies are effective on paraffin-embedded tissue7. Monoclonal antibodies 123C3 and MOC-1 recognise non-carbohydrate epitopes. JLP5B9 recognises the polysialated epitopes of embryonic NCAM (eNCAM)10.

Immunohistochemical expression

Normal tissues:

• thyroid follicular epithelium, hepatocytes, renal tubules10

• in the stomach, parietal and scattered neuroendocrine cells show strong membrane staining12. Nerve and muscle fibres stain strongly while the muscularis mucosae and muscularis propria stain weakly12.

• myometrium stains weakly12

• The smooth muscle of the bladder stains weakly12

• Atrophic skeletal muscle fibres stain strongly12.

Neoplasms:

• see comparison of neuroendocrine markers

• pulmonary small cell carcinoma

• mesothelioma:2

• carcinoid

• rarely positive in pulmonary and laryngeal squamous cell carcinoma

• pancreatic islet cell tumour

• Pancreatic tumours with neuroendocrine differentiation

• Merkel cell carcinoma

• hepatocellular carcinoma

• some renal cell carcinoma1

• some ovarian carcinoma1

• some endometrial carcinoma1

• follicular and papillary thyroid carcinoma

• neuroblastoma

• ganglioglioma

• oligodendroglioma

• glioblastoma multiforme

• phaeochromocytoma

• retinoblastoma

• large granular lymphocyte leukaemia of NK type

• myeloma

• natural killer cells and a subset of T-lymphocytes

• osteoblasts9

• Using a polyclonal antibody, there is immunoreactivity in the fetal myocardium, the conduction system of the adult heart, and upregulation in Chagas' disease, where staining of intercalated disks and amastigote nests is seen4.

• Perisinusoidal stellate cells of the liver5.

• Ovarian sex cord stromal tumours: 16/1811 adult granulosa cell tumours, 2/211 juvenile granulosa cell tumours, 2/211 malignant Sertoli cell tumours.

The following are negative for CD 56:

• nasopharyngeal carcinoma

• colonic carcinoma

• melanoma

• meningioma

• follicle centre cell lymphoma

• hairy cell leukaemia

• Ewing's sarcoma

• GIST is usually negative, while its mimics with the gastrointestinal tract are commonly positive. Positivity may be more common in malignant than in benign GISTs:

Diagnostic utility

• identification of pulmonary small cell carcinomas. CD56 may be particularly useful in crushed biopsies, as crushed areas of small cell carcinoma retain staining for CD56, while staining for TTF-1 and MNF116 tend to be lost13. By comparison, crushed lymphoid tissue retains staining for CD45, for which crushed small cell carcinoma is negative13.

• CD56 may be useful in differentiating myeloma from MGUS and polyclonal plasmacytosis

References

1 Kaufmann, O. Georgi, T. Dietel, M. Utility of 123C3 monoclonal antibody against CD56 (NCAM) for the diagnosis of small cell carcinomas on paraffin sections. Hum Pathol 1997;28:1373-8.

2 Lantuejoul S. Laverriere MH. Sturm N. Moro D. Frey G. Brambilla C. Brambilla E. NCAM (neural cell adhesion molecules) expression in malignant mesotheliomas. Human Pathology 2000;31(4):415-21.

3 Al-Khafaji et al. Immunohistologic analysis of gastrointestinal and pulmonary carcinoid tumours. Human Pathol 1998;29:992-999.

4 Soler, A. P., Gilliard, G., Xiong, Y., Knudsen, K. A., Martin, J. L., De Suarez, C. B., Mota Gamboa, J. D., Mosca, W., Zoppi, L. B. Overexpression of neural cell adhesion molecule in Chagas' myocarditis. Human Pathol 2001;32:149-155.

5 Nakatani, K., Seki, S., Kawada, N., Kobayashi, K., Kaneda, K. Expression of neural cell adhesion molecule (N-CAM) in perisinusoidal stellate cells of the human liver. Cell Tissue Res 1996;283:159-165.

6 Naka, T., Oda, Y., Iwamoto, Y. Immunohistochemical analysis of E-cadherin, alpha-catenin, beta- catenin, gamma-catenin, and neural cell adhesion molecule (NCAM) in chordoma. J Clin Pathol 2001;54:945-950

7 Leong A S-Y, Cooper K and Leong FJ W-M. Manual of diagnostic antibodies for immunohistology. 2nd edition, 2003

8 Martin, P., A. Santon, et al. (2004). "Neural cell adhesion molecule expression in plasma cells in bone marrow biopsies and aspirates allows discrimination between multiple myeloma, monoclonal gammopathy of uncertain significance and polyclonal plasmacytosis." Histopathology 44(4): 375-80.

9 Ely, S. A. and D. M. Knowles (2002). "Expression of CD56/neural cell adhesion molecule correlates with the presence of lytic bone lesions in multiple myeloma and distinguishes myeloma from monoclonal gammopathy of undetermined significance and lymphomas with plasmacytoid differentiation." Am J Pathol 160(4): 1293-9.

10 Ionescu DN, Treaba D, Gilks CB, et al. Nonsmall cell lung carcinoma with neuroendocrine differentiation--an entity of no clinical or prognostic significance. Am J Surg Pathol 2007; 31:26-32

11 Kingston GT,Manek S. CD56 immunoreactivity in ovarian sex cord-stromal tumours. Histopathology 2007; 51:723-5

12 Agaimy A,Wunsch PH Distribution of neural cell adhesion molecule (NCAM/CD56) in gastrointestinal stromal tumours and their intra-abdominal mesenchymal mimics. J Clin Pathol 2008; 61:499-503

13 Kontogianni K, Nicholson AG, Butcher D, et al. CD56: a useful tool for the diagnosis of small cell lung carcinomas on biopsies with extensive crush artefact. J Clin Pathol 2005; 58:978-80

This page last revised 20.12.2008.

©SMUHT/PW Bishop