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A monoclonal antibody against SV 40 large T antigen ( PA b416) does not label Merkel cell carcinoma
Author(s) -
Pelletier Daniel J,
Czeczok Thomas W,
Bellizzi Andrew M
Publication year - 2018
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13483
Subject(s) - merkel cell polyomavirus , merkel cell carcinoma , immunohistochemistry , antigen , merkel cell , clone (java method) , pathology , monoclonal antibody , biology , antibody , epitope , carcinoma , medicine , immunology , dna , genetics
Aims Merkel cell carcinoma represents poorly differentiated neuroendocrine carcinoma of cutaneous origin. In most studies, the vast majority of Merkel cell carcinomas are Merkel cell polyomavirus ( MCP yV)‐associated. SV 40 polyomavirus immunohistochemistry is typically used in the diagnosis of other polyomavirus‐associated diseases, including tubulointerstitial nephritis and progressive multifocal leukoencephalopathy, given cross‐reactivity with BK and JC polyomaviruses. MCP yV‐specific immunohistochemistry is commercially available, but, if antibodies against SV 40 also cross‐reacted with MCP yV, that would be advantageous from a resource‐utilisation perspective. Methods and results Tissue microarrays were constructed from 39 Merkel cell carcinomas, 24 small‐cell lung carcinomas, and 18 extrapulmonary visceral small‐cell carcinomas. SV 40 large T antigen immunohistochemistry (clone PA b416) was performed; MCP yV large T antigen immunohistochemistry (clone CM 2B4) had been previously performed. UniProt was used to compare the amino acid sequences of the SV 40, BK , JC and MCPyV large T antigens, focusing on areas recognised by the PA b416 and CM 2B4 clones. SV 40 immunohistochemistry was negative in all tumours; MCP yV immunohistochemistry was positive in 38% of Merkel cell carcinomas and in 0% of non‐cutaneous poorly differentiated neuroendocrine carcinomas. UniProt analysis revealed a high degree of similarity between SV 40, BK , and JC viruses in the region recognised by PA b416. There was less homology between SV 40 and MCP yV in this region, which was also interrupted by two long stretches of amino acids unique to MCP yV. The CM 2B4 clone recognises a unique epitope in one of these stretches. Conclusions The PAb416 antibody against the SV 40 large T antigen does not cross‐react with MCP yV large T antigen, and thus does not label Merkel cell carcinoma.