Association of expression of the hedgehog signal with Merkel cell polyomavirus infection and prognosis of Merkel cell carcinoma.
AffiliationDivision of Molecular Pathology, Department of Pathology, Tottori University Faculty of Medicine, Yonago, 683-8503, Japan
MetadataShow full item record
AbstractMerkel 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. 29 MCPyV-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. PCR 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, and Japanese ethnicity were associated with better overall survival (P=.034, P=.001, P=.042, P=.036, respectively). Higher expression of SHH and MCPyV infection were associated with improved MCC-specific survival (P=.037, 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 two mutations with amino acid changes were detected in MCPyV-negative MCCs only: one missense mutation in GLI1 exon 4 and one 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.
CitationAssociation of expression of the hedgehog signal with Merkel cell polyomavirus infection and prognosis of Merkel cell carcinoma. 2017 Hum Pathol
- Lower expression of CADM1 and higher expression of MAL in Merkel cell carcinomas are associated with Merkel cell polyomavirus infection and better prognosis.
- Authors: Iwasaki T, Matsushita M, Nonaka D, Nagata K, Kato M, Kuwamoto S, Murakami I, Hayashi K
- Issue date: 2016 Feb
- Comparison of Akt/mTOR/4E-BP1 pathway signal activation and mutations of PIK3CA in Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative carcinomas.
- Authors: Iwasaki T, Matsushita M, Nonaka D, Kuwamoto S, Kato M, Murakami I, Nagata K, Nakajima H, Sano S, Hayashi K
- Issue date: 2015 Feb
- Decreased H3K27me3 Expression Is Associated With Merkel Cell Polyomavirus-negative Merkel Cell Carcinoma, Especially Combined With Cutaneous Squamous Cell Carcinoma.
- Authors: Matsushita M, Iwasaki T, Wardhani LO, Kuwamoto S, Nonaka D, Nagata K, Kato M, Kitamura Y, Hayashi K
- Issue date: 2019 Oct
- Mutational landscape of MCPyV-positive and MCPyV-negative Merkel cell carcinomas with implications for immunotherapy.
- Authors: Goh G, Walradt T, Markarov V, Blom A, Riaz N, Doumani R, Stafstrom K, Moshiri A, Yelistratova L, Levinsohn J, Chan TA, Nghiem P, Lifton RP, Choi J
- Issue date: 2016 Jan 19
- Correlation of Merkel cell polyomavirus positivity with PDGFRα mutations and survivin expression in Merkel cell carcinoma.
- Authors: Batinica M, Akgül B, Silling S, Mauch C, Zigrino P
- Issue date: 2015 Jul