PMID- 28174236
OWN - NLM
STAT- MEDLINE
DCOM- 20180409
LR  - 20180409
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 23
IP  - 14
DP  - 2017 Jul 15
TI  - Merkel Cell Carcinomas Arising in Autoimmune Disease Affected Patients Treated 
      with Biologic Drugs, Including Anti-TNF.
PG  - 3929-3934
LID - 10.1158/1078-0432.CCR-16-2899 [doi]
AB  - 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. (c)2017 AACR.
CI  - (c)2017 American Association for Cancer Research.
FAU - Rotondo, John Charles
AU  - Rotondo JC
AD  - Department of Morphology, Surgery and Experimental Medicine, School of Medicine, 
      University of Ferrara, Ferrara, Italy.
FAU - Bononi, Ilaria
AU  - Bononi I
AD  - Department of Morphology, Surgery and Experimental Medicine, School of Medicine, 
      University of Ferrara, Ferrara, Italy.
FAU - Puozzo, Andrea
AU  - Puozzo A
AD  - Department of Morphology, Surgery and Experimental Medicine, School of Medicine, 
      University of Ferrara, Ferrara, Italy.
FAU - Govoni, Marcello
AU  - Govoni M
AD  - Department of Medical Sciences, School of Medicine, University of Ferrara, 
      Ferrara, Italy.
FAU - Foschi, Valentina
AU  - Foschi V
AD  - Department of Medical Sciences, School of Medicine, University of Ferrara, 
      Ferrara, Italy.
FAU - Lanza, Giovanni
AU  - Lanza G
AD  - Department of Medical Sciences, School of Medicine, University of Ferrara, 
      Ferrara, Italy.
FAU - Gafa, Roberta
AU  - Gafa R
AD  - Department of Morphology, Surgery and Experimental Medicine, School of Medicine, 
      University of Ferrara, Ferrara, Italy.
FAU - Gaboriaud, Pauline
AU  - Gaboriaud P
AD  - Universite Francois Rabelais, UMR INRA 1282 ISP, Faculte des Sciences 
      Pharmaceutiques, Tours, France.
FAU - Touze, Francoise Antoine
AU  - Touze FA
AD  - Universite Francois Rabelais, UMR INRA 1282 ISP, Faculte des Sciences 
      Pharmaceutiques, Tours, France.
FAU - Selvatici, Rita
AU  - Selvatici R
AD  - Department of Medical Sciences, School of Medicine, University of Ferrara, 
      Ferrara, Italy.
FAU - Martini, Fernanda
AU  - Martini F
AD  - Department of Morphology, Surgery and Experimental Medicine, School of Medicine, 
      University of Ferrara, Ferrara, Italy. mauro.tognon@unife.it 
      fernanda.martini@unife.it.
FAU - Tognon, Mauro
AU  - Tognon M
AD  - Department of Morphology, Surgery and Experimental Medicine, School of Medicine, 
      University of Ferrara, Ferrara, Italy. mauro.tognon@unife.it 
      fernanda.martini@unife.it.
LA  - eng
PT  - Journal Article
DEP - 20170207
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antibodies)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Antigens, Viral)
RN  - 0 (Antigens, Viral, Tumor)
RN  - 0 (Biological Products)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Aged
MH  - Antibodies/*blood/immunology
MH  - Antigens, Neoplasm/blood/immunology
MH  - Antigens, Viral/blood
MH  - Antigens, Viral, Tumor/blood
MH  - Arthritis, Rheumatoid/complications/drug therapy/immunology
MH  - Biological Products/adverse effects/*immunology/therapeutic use
MH  - Carcinogenesis
MH  - Carcinoma, Merkel Cell/*blood/chemically induced/immunology/virology
MH  - Female
MH  - Humans
MH  - Male
MH  - Merkel cell polyomavirus/immunology/pathogenicity
MH  - Middle Aged
MH  - Spondylitis, Ankylosing/complications/drug therapy/immunology
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/*immunology/therapeutic use
EDAT- 2017/02/09 06:00
MHDA- 2018/04/10 06:00
CRDT- 2017/02/09 06:00
PHST- 2016/11/17 00:00 [received]
PHST- 2017/01/17 00:00 [revised]
PHST- 2017/01/18 00:00 [accepted]
PHST- 2017/02/09 06:00 [pubmed]
PHST- 2018/04/10 06:00 [medline]
PHST- 2017/02/09 06:00 [entrez]
AID - 1078-0432.CCR-16-2899 [pii]
AID - 10.1158/1078-0432.CCR-16-2899 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2017 Jul 15;23(14):3929-3934. doi: 
      10.1158/1078-0432.CCR-16-2899. Epub 2017 Feb 7.