Clinicopathological Characterization of MCPyV-Infected Merkel Cell Carcinomas in Japan and United Kingdom
Michiko Matsushita, Takeshi Iwasaki, Daisuke Nonaka, Hideki Nakajima, Satoshi Kuwamoto, Masako Kato, Ichiro Murakami, Shigetoshi Sano, Yukisato Kitamura, Kazuhiko Hayashi. Tottori University, Yonago, Tottori, Japan; Christie Hospital, NHS Foundation Trust, Manchester, United Kingdom; Kochi University, Nankoku, Kochi, Japan
Background: Merkel cell polyomavirus (MCPyV) is a novel polyomavirus that is monoclonally integrated into genomes of up to 80% of Merkel cell carcinomas (MCC). The original association between MCPyV and MCC tumors has been confirmed in several countries. The aims of this study are to establish the MCPyV phylogenetic tree and clarify the molecular and clinicopathological differences between Japanese and Caucasian MCCs.
Design: We analyzed 45 Japanese [women:31, men:11] and 22 Caucasian (UK) [women:17, men:5] MCC cases. To detect MCPyV-DNA and mRNA expression of Small T (ST) and Large T (LT) antigen, we performed real-time PCR. Analyzed whole sequences of MCPyV-LT and -ST antigen using direct sequence were assembled and compared to 50 known MCPyV sequences from NCBI database. Then we establish a phylogenetic tree. Immunohistochemical analyses were performed using CM2B4 (anti-LT antibody) and ISH was also done using DNA and RNA probes targeting ST or LT mRNA.
Results: Rate of MCPyV infection was significantly lower in UK MCCs [32% (7/22)] than Japanese MCCs [76% (34/45)] (p=0.001). Combined MCC and SqCC was observed more frequently in UK. Phylogenetic analysis of data base indicated three main clades (Asian clade and Western clades). All 7 sequences of MCPyV from Japanese MCCs clustered in Asian clade. However, there was no significant differences in MCPyV copy numbers, expressions of LT and ST mRNA and frequency of CM2B4 positivity between MCPyV-positive cases in Japan and UK. The favorable MCC-specific survival was longer in MCPyV-positive MCCs than MCPyV-negative MCCs, but the difference was not statistically significant. Expression levels of ST or LT mRNA were not associated with significant differences in prognosis. The details of ISH will be shown in the congress.
Conclusions: MCPyV-positive ratio was significantly higher in Japanese than UK MCCs. All 7 MCPyV sequences from Japanese MCCs were belonged to Asian clade. However, MCPyV quantity, LT and ST mRNA expression and LT expression between Japanese and UK–positive cases were neither different and nor associated with prognosis.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 61, Wednesday Morning