Detection of Merkel cell polyomavirus in cervical squamous cell carcinomas and adenocarcinomas from Japanese patients

• Published in: Virology journal Vol. 9; no. 1; p. 154
• Main Authors: Imajoh, Masayuki, Hashida, Yumiko, Nemoto, Yuiko, Oguri, Hiroyoshi, Maeda, Nagamasa, Furihata, Mutsuo, Fukaya, Takao, Daibata, Masanori
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 09.08.2012; BioMed Central; BMC
• Subjects: Adenocarcinoma; Adenocarcinoma - pathology; Adenocarcinoma - virology; Adenylate cyclase; Amino Acid Sequence; Amino acid substitution; Analysis; Antigens, Viral, Tumor - genetics; Antigens, Viral, Tumor - metabolism; Asian Continental Ancestry Group; Base Sequence; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - virology; Cervical adenocarcinoma; Cervical cancer; Cervical squamous cell carcinoma; Cervix; Deoxyribonucleic acid; DNA; DNA, Viral; Epidemiology; Female; Genomes; Genomics; Genotyping; HPV typing; Human papillomavirus; Humans; Immunohistochemistry; Japan; Malignancy; Merkel cell polyomavirus; Merkel cell polyomavirus - classification; Merkel cell polyomavirus - genetics; Merkel cell polyomavirus - isolation & purification; Molecular Sequence Data; Molecular Typing; Papillomavirus infections; Patients; Polyclonal antibodies; Polymerase chain reaction; Polyomavirus; Polyomavirus Infections - diagnosis; Proteins; Sequence Alignment; Sequence Analysis, DNA; Skin; Skin cancer; Squamous cell carcinoma; Tumor cells; Tumor Virus Infections - diagnosis; Tumors; Uterine cancer; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology; Uterus; Viral proteins; VP1 protein; Japan
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/1743-422x-9-154

Merkel cell polyomavirus (MCPyV) was identified originally in Merkel cell carcinoma (MCC), a rare form of human skin neuroendocrine carcinoma. Evidence of MCPyV existence in other forms of malignancy such as cutaneous squamous cell carcinomas (SCCs) is growing. Cervical cancers became the focus of our interest in searching for potentially MCPyV-related tumors because: (i) the major histological type of cervical cancer is the SCC; (ii) the uterine cervix is a common site of neuroendocrine carcinomas histologically similar to MCCs; and (iii) MCPyV might be transmitted during sexual interaction as demonstrated for human papillomavirus (HPV). In this study, we aimed to clarify the possible presence of MCPyV in cervical SCCs from Japanese patients. Cervical adenocarcinomas (ACs) were also studied. Formalin-fixed paraffin-embedded tissue samples from 48 cervical SCCs and 16 cervical ACs were examined for the presence of the MCPyV genome by polymerase chain reaction (PCR) and sequencing analyses. PCR analysis revealed that 9/48 cervical SCCs (19%) and 4/16 cervical ACs (25%) were positive for MCPyV DNA. MCPyV-specific PCR products were sequenced to compare them with reference sequences. The nucleotide sequences in the MCPyV large T (LT)-sequenced region were the same among MCPyV-positive cervical SCCs and AC. Conversely, in the MCPyV viral protein 1 (VP1)-sequenced region, two cervical SCCs and three cervical ACs showed several nucleotide substitutions, of which three caused amino acid substitutions. These sequencing results suggested that three MCPyV variants of the VP1 were identified in our cases. Immunohistochemistry showed that the LT antigen was expressed in tumor cells in MCPyV-positive samples. Genotyping of human HPV in the MCPyV-positive samples revealed that infected HPVs were HPV types 16, 31 and 58 for SCCs and HPV types 16 and 18 for ACs. This study provides the first observation that MCPyV coexists in a subset of HPV-associated cervical cancers from Japanese patients. The prevalence of MCPyV in these lesions was close to that observed in the cutaneous SCCs. Further worldwide epidemiological surveys are warranted to determine the possible association of MCPyV with pathogenesis of cervical cancers.