A Monoclonal Antibody to SV40 Large T Antigen (PAb416) Does Not Label Merkel Cell Carcinoma

Abstract

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 (MCPyV)-associated. SV40 polyomavirus immunohistochemistry is typically used in the diagnosis other polyomavirus-associated diseases including tubulointerstitial nephritis and progressive multifocal leukoencephalopathy, given cross-reactivity with BK and JC polyomaviruses. MCPyV-specific immunohistochemistry is commercially available, but if SV40 immunohistochemistry also cross-reacted with MCPyV that would be advantageous from a resource-utilization 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. SV40 large T antigen immunohistochemistry (clone PAb416) was performed; MCPyV large T antigen immunohistochemistry (clone CM2B4) had been previously performed. UniProt was used to compare the amino acid sequences of the SV40, BK, JC, and Merkel cell polyomavirus large T antigens, focusing on areas recognized by the PAb416 and CM2B4 clones. SV40 immunohistochemistry was negative in all tumors; MCPyV immunohistochemistry was positive in 38% of Merkel cell carcinomas and 0% of non-cutaneous poorly differentiated neuroendocrine carcinomas. UniProt analysis revealed a high degree of similarity between SV40, BK, and JC viruses in the region recognized by PAb416. There was less homology between SV40 and MCPyV in this region, which was also interrupted by 2 long stretches of amino acids unique to MCPyV. The CM2B4 clone recognizes a unique epitope in one of these stretches.

Conclusions

SV40 large T antigen immunohistochemistry does not cross react with MCPyV large T antigen and, thus, does not label Merkel cell carcinoma.

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