title: Detection of Merkel cell polyomavirus in cervical squamous cell carcinomas and adenocarcinomas from Japanese patients.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Microbiology and Infection, Kochi Medical School, Kochi University, Nankoku, Kochi, 783-8505, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Imajoh
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Hashida
authors.forename: Yuiko
authors.initials: Y
authors.lastname: Nemoto
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Oguri
authors.forename: Nagamasa
authors.initials: N
authors.lastname: Maeda
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Furihata
authors.forename: Takao
authors.initials: T
authors.lastname: Fukaya
authors.forename: Masanori
authors.initials: M
authors.lastname: Daibata
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000821:virology*; D000595:Amino Acid Sequence; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000378:metabolism; D044466:Asian People; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral; D005260:Female; D006801:Humans; D007564:Japan; D059965:Merkel cell polyomavirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D008969:Molecular Sequence Data; D058889:Molecular Typing; D027601:Polyomavirus Infections / Q000175:diagnosis*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014412:Tumor Virus Infections / Q000175:diagnosis*; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*
chemical_list: D000957:Antigens, Viral, Tumor; D004279:DNA, Viral