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

作者：Higaki Mori Hiromi^*; Kuwamoto Satoshi; Iwasaki Takeshi; Kato Masako; Murakami Ichiro; Nagata Keiko; Sano Hitoshi; Horie Yasushi; Yoshida Yuichi; Yamamoto Osamu; Adachi Kaori; Nanba Eiji; Hayashi Kazuhiko

来源：Human Pathology, 2012, 43(12): 2282-2291.

DOI：10.1016/j.humpath.2012.04.002

• Merkel cell polyomavirus
• Merkel cell carcinoma
• Clinicopathological differences
• TP53 mutation

Merkel cell polyomavirus is a novel polyomavirus that is monoclonally integrated into genomes of up to 80% of human Merkel cell carcinomas. Merkel cell polyomavirus positive Merkel cell carcinomas showed less metastatic tendency and better prognosis according to some reports, whereas others disagree. In this study, we analyzed clinicopathological characteristics of 20 Merkel cell polyomavirus positive and 6 Merkel cell polyomavirus negative Merkel cell carcinoma cases, in which we already reported the association of Merkel cell polyomavirus infection with statistically significant morphological differences. Immunohistochemical expressions of cell cycle related proteins, mutations of the TP53 tumor-suppressor gene (exons 4-9) and p14ARF promoter methylation status as well as detailed clinical data were analyzed and compared between Merkel cell polyomavirus positive and Merkel cell polyomavirus negative cases. Merkel cell polyomavirus positive Merkel cell carcinomas showed better prognosis with one spontaneous regression case and significantly higher expression of retinoblastoma protein (P = .0003) and less p53 expression (P = .0005) compared to Merkel cell polyomavirus-negative Merkel cell carcinomas. No significant differences were found in expressions of p63, MDM2, p14ARF or MIB-1 index, and p14ARF promoter methylation status. Interestingly, frequency of TP53 non-ultraviolet signature mutation was significantly higher in Merkel cell polyomavirus negative Merkel cell carcinomas than in Merkel cell polyomavirus positive Merkel cell carcinomas (P = .036), whereas no significant difference was detected in TP53 ultraviolet signature mutations between two groups. These results suggest that Merkel cell polyomavirus positive and negative Merkel cell carcinomas likely develop through different tumorigenic pathways and that the presence or absence of Merkel cell polyomavirus in the tumor is still an important factor that affects survival in patients with Merkel cell carcinoma.

• 出版日期2012-12