Merkel cell polyomavirus is implicated in a subset of Merkel cell carcinomas, in the Indian subcontinent

Abstract

Merkel cell carcinoma is a rare, lethal cancer histopathologically composed of cells showing similarity with mechanoreceptor Merkel cells. Merkel cell tumors manifest in two distinct forms. While a virus called Merkel cell polyomavirus is involved in the pathogenesis of one form of Merkel tumors, the other is driven by ultraviolet (UV)-linked mutations. In this study we investigated 18 cases, from the Indian population, of Merkel cell carcinoma for immunohistochemical (IHC) expression of Merkel cell polyomavirus (MCV) T antigen, including 12 cases tested by PCR, to identify viral etiopathology. We tested the tumors with two sensitive antibodies (CM2B4 and Ab3), targeting the viral large T antigen protein and with PCR primers targeting the N terminus of T antigen. Overall, we observed 38.8% (7/18) tumors displaying positive IHC expression of Merkel cell polyomavirus T antigen and 25% (3/12) tumors showing positive results, by both, immunohistochemistry and PCR. This constitutes the first report from India showing implication of MCV in Merkel cell carcinomas. Moreover, this is one of the larger series of Merkel cell carcinomas, tested for MCV, by both immunohistochemistry and PCR, in this part of the world. These results further indicate that a slightly more number of such cases in India are likely to be caused by UV-linked damage, as opposed to Merkel cell polyomavirus mediated tumorigenesis, which is definitely implicated in a subset of cases.

Keywords: MCC; MCV; Merkel cell carcinoma; Polyomavirus; T antigen.

Fig. 1. Merkel cell polyomavirus positive Merkel cell carcinoma.

7 cases of Merkel cell carcinoma were found positive for Merkel cell polyomavirus. H&E staining shows epidermis with a tumor below composed of malignant round cells, medium power. Tumor cells show MCV Large T antigen positivity ranging from strong positivity (cases #2, #4, #7, #17 and #18) to weak/focal positivity (cases #12 and #13). Image for Cases #18 is of CM2B4 staining, as it was not tested with Ab3.