Association of Merkel cell polyomavirus infection with morphologic differences in Merkel cell carcinoma

Satoshi Kuwamoto, Hiromi Higaki, Kyosuke Kanai, Takeshi Iwasaki, Hitoshi Sano, Keiko Nagata, Kaoru Kato, Masako Kato, Ichiro Murakami, Yasushi Horie, Osamu Yamamoto, Kazuhiko Hayashi

Research output: Contribution to journalArticlepeer-review

86 Citations (Scopus)

Abstract

Recently, it has been shown that approximately 80% of Merkel cell carcinomas harbor a novel polyomavirus named Merkel cell polyomavirus, thought to be a carcinogenic agent. However, it is not fully elucidated whether Merkel cell carcinomas differ with regard to the presence or absence of Merkel cell polyomavirus. To address this, we investigated morphologic differences between Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas by morphometry. Using polymerase chain reaction and real-time quantitative polymerase chain reaction, Merkel cell polyomavirus was detected in 20 (77%) of 26 Merkel cell carcinoma cases, including 4 Merkel cell carcinomas combined with squamous cell carcinomas. Interestingly, Merkel cell polyomavirus was detected only in ordinary (pure) Merkel cell carcinomas; none of the 4 combined Merkel cell carcinomas + squamous cell carcinomas was positive for Merkel cell polyomavirus (P = .001). Morphometric analyses revealed that Merkel cell polyomavirus-negative Merkel cell carcinomas had more irregular nuclei (P < .001) and more abundant cytoplasm (P = .001) than Merkel cell polyomavirus-positive Merkel cell carcinomas, which had uniform round nuclei and scant cytoplasm. Reliability of the morphometry was confirmed using intraobserver and interobserver reliability tests. These results demonstrated statistically significant differences in tumor cell morphology between Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas and reconfirmed the absence of Merkel cell polyomavirus in combined tumors. Furthermore, the results strongly suggest fundamental biological differences between Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas, supporting that Merkel cell polyomavirus plays an important role in the pathogenesis of Merkel cell polyomavirus-positive Merkel cell carcinoma.

Original languageEnglish
Pages (from-to)632-640
Number of pages9
JournalHuman Pathology
Volume42
Issue number5
DOIs
Publication statusPublished - May 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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