Association of expression of the hedgehog signal with Merkel cell polyomavirus infection and prognosis of Merkel cell carcinoma

Teruyuki Kuromi, Michiko Matsushita, Takeshi Iwasaki, Daisuke Nonaka, Satoshi Kuwamoto, Keiko Nagata, Masako Kato, Gen Akizuki, Yukisato Kitamura, Kazuhiko Hayashi

研究成果: Contribution to journalArticle査読

15 被引用数 (Scopus)

抄録

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer that mostly occurs in the elderly. Merkel cell polyomavirus (MCPyV) is detected in approximately 80% of MCCs and is associated with carcinogenesis. Hedgehog signaling pathway plays a role in human embryogenesis and organogenesis. In addition, reactivation of this pathway later in life can cause tumors. Twenty-nineMCPyV-positive and 21 MCPyV-negative MCCs were immunohistochemically stained with primary antibodies for hedgehog signaling (SHH, IHH, PTCH1, SMO, GLI1, GLI2, and GLI3) and evaluated using H-score. Polymerase chain reaction and sequence analysis for SHH and GLI1 exons were also performed. Expression of SHH was higher in MCPyV-positive MCCs than in MCPyV-negative MCCs (P <.001). Higher expression of GLI1, MCPyV infection, male sex, and Japanese ethnicity were associated with better overall survival (P =.034, P =.001, P =.042, and P =.036, respectively). Higher expression of SHH and MCPyV infection were associated with improved MCC-specific survival (P =.037 and P =.002, respectively). The mutation analysis of prognosis-related GLI1 and SHH genes in our study revealed a low frequency of mutations in the 10 exons examined, except GLI1 exon 5 (18/22 cases), all having the same silent mutation of c.576G>A. Only 2 mutations with amino acid changes were detected in MCPyV-negative MCCs only: 1 missense mutation in GLI1 exon 4 and 1 nonsense mutation in SHH-3B. Expression of SHH and GLI1 may be useful prognostic markers of MCC because increased expression was associated with better prognosis. The high rate of c.576G>A silent mutation in GLI1 exon 5 was a feature of MCC.

本文言語英語
ページ(範囲)8-14
ページ数7
ジャーナルHuman Pathology
69
DOI
出版ステータス出版済み - 11 2017

All Science Journal Classification (ASJC) codes

  • 病理学および法医学

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