Merkel Cell Carcinomas arising in autoimmune disease affected patients treated with biological drugs, including TNF.

Abstract

Purpose: The purpose of this investigation was to characterize Merkel cell carcinomas (MCC) arising in patients affected by auto-immune diseases, treated with biologic drugs. Experimental Design: Serum samples from MCC patients were analyzed for the presence and titer of antibodies against antigens of the oncogenic Merkel cell polyomavirus (MCPyV). IgG antibodies against the viral oncoproteins Large T (LT) and small t (ST) antigens and the viral capsid protein 1 were analyzed by indirect E.L.I.S.As. Viral antigens were recombinant LT/ST and virus-like particles (VLPs), respectively. MCPyV DNA sequences were studied using PCR methods in MCC tissues and in peripheral blood mononuclear cells (PBMCs). Immuno-histochemical analyses were carried out in MCC tissues to reveal MCPyV LT oncoprotein. Results: MCPyV DNA sequences identified in MCC tissues showed 100% homology with the European MKL-1 strain. PBMCs from patients tested MCPyV-negative. Viral DNA loads in the three MCC tissues were in the 0.1-30 copy/cell range. IgG antibodies against LT/ST were detected in patients 1 and 3, whereas patient 2 did not react to the MCPyV LT/ST antigen. Sera from the three MCC patients contained IgG antibodies against MCPyV VP1. MCC tissues tested MCPyV LT-antigen positive in HIC assays, with strong LT expression with diffuse nuclear localization. Normal tissues tested MCPyV LT-negative when employed as control. Conclusions: We investigated 3 new MCCs in patients affected by rheumatologic diseases treated with biologic drugs, incuding TNF. A possible cause-effect relationship between pharmacological immunosuppressive treatment and MCC onset is suggested. Indeed, MCC is associated with MCPyV LT oncoprotein activity.