Merkel Cell Carcinomas Arising in Autoimmune Disease Affected Patients Treated with Biologic Drugs, Including Anti-TNF.
Purpose:The purpose of this investigation was to characterize Merkel cell carcinomas (MCC) arisen in patients affected by autoimmune diseases and treated with biologic drugs.Experimental Design:Serum samples from patients with MCC 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 ELISA. Viral antigens were recombinant LT/ST and virus-like particles (VLP), respectively. MCPyV DNA sequences were studied using PCR methods in MCC tissues and in peripheral blood mononuclear cells (PBMC). Immunohistochemical (IHC) 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 to 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 patients with MCC contained IgG antibodies against MCPyV VP1. MCC tissues tested MCPyV LT-antigen-positive in IHC assays, with strong LT expression with diffuse nuclear localization. Normal tissues tested MCPyV LT-negative when employed as control.Conclusions:We investigated three new MCCs in patients affected by rheumatologic diseases treated with biologic drugs, including TNF. A possible cause-effect relationship between pharmacologic immunosuppressive treatment and MCC onset is suggested. Indeed, MCC is associated with MCPyV LT oncoprotein activity.Clin Cancer Res; 23(14); 3929-34. ©2017 AACR.
Department of Morphology, Surgery and Experimental Medicine, School of Medicine, University of Ferrara, Ferrara, Italy.
John Charles
JC
Rotondo
Department of Morphology, Surgery and Experimental Medicine, School of Medicine, University of Ferrara, Ferrara, Italy.
Ilaria
I
Bononi
Department of Morphology, Surgery and Experimental Medicine, School of Medicine, University of Ferrara, Ferrara, Italy.
Andrea
A
Puozzo
Department of Medical Sciences, School of Medicine, University of Ferrara, Ferrara, Italy.
Marcello
M
Govoni
Department of Medical Sciences, School of Medicine, University of Ferrara, Ferrara, Italy.
Valentina
V
Foschi
Department of Medical Sciences, School of Medicine, University of Ferrara, Ferrara, Italy.
Giovanni
G
Lanza
Department of Morphology, Surgery and Experimental Medicine, School of Medicine, University of Ferrara, Ferrara, Italy.
Roberta
R
Gafà
Université Francois Rabelais, UMR INRA 1282 ISP, Faculté des Sciences Pharmaceutiques, Tours, France.
Pauline
P
Gaboriaud
Université Francois Rabelais, UMR INRA 1282 ISP, Faculté des Sciences Pharmaceutiques, Tours, France.
Françoise Antoine
FA
Touzé
Department of Medical Sciences, School of Medicine, University of Ferrara, Ferrara, Italy.
Rita
R
Selvatici
Department of Morphology, Surgery and Experimental Medicine, School of Medicine, University of Ferrara, Ferrara, Italy. mauro.tognon@unife.it fernanda.martini@unife.it.
Fernanda
F
Martini
Department of Morphology, Surgery and Experimental Medicine, School of Medicine, University of Ferrara, Ferrara, Italy. mauro.tognon@unife.it fernanda.martini@unife.it.
Mauro
M
Tognon
D000368:Aged; D000906:Antibodies / Q000097:blood* / Q000276:immunology; D000951:Antigens, Neoplasm / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000097:blood; D000957:Antigens, Viral, Tumor / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D001688:Biological Products / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D063646:Carcinogenesis; D015266:Carcinoma, Merkel Cell / Q000097:blood* / Q000139:chemically induced / Q000276:immunology / Q000821:virology; D005260:Female; D006801:Humans; D008297:Male; D059965:Merkel cell polyomavirus / Q000276:immunology / Q000472:pathogenicity; D008875:Middle Aged; D013167:Spondylitis, Ankylosing / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000627:therapeutic use
D000906:Antibodies; D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D000957:Antigens, Viral, Tumor; D001688:Biological Products; D014409:Tumor Necrosis Factor-alpha