Analysis of pathogenesis using NGS in Merkel cell carcinoma associated polyomavirus

• Project/Area Number: 26860238
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Tottori University
• Principal Investigator: Matsushita Michiko 鳥取大学, 医学部, 助教 (70642198)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: メルケル細胞癌 / MCPyV / Immunohistochemistry / CADM1 / Hedgehog signal経路 / JAK-STAT経路 / immunohistochemistry / NGS

Outline of Final Research Achievements

Merkel cell carcinoma (MCC) is a malignant neuroendocrine skin tumor that occurs most often in elderly patients. Approximately 80% of MCCs harbor Merkel cell polyomavirus (MCPyV), thought to be a carcinogenic agent. In this study, MCPyV-negative MCCs significantly expressed higher CADM1 and lower MAL than MCPyV-positive MCCs and related to unfavorable outcomes in MCCs. In hedgehog signaling pathway, increased SHH and GLI1 expression was associated with better prognosis. JAK-STAT signaling pathway was expressed in MCCs. Therefore, we suggest that these factors may play a important role in tumorigenesis of MCCs.

Research Products

• [Journal Article] Comment on 'Cytokeratin 20-negative Merkel cell carcinoma is infrequently associated with the Merkel cell polyomavirus'. (2016)
  • Author(s): Iwasaki T, Matsushita M, Nonaka D, Murakami I, Hayashi K.
  • Journal Title: Mod Pathol. Volume: 29 Issue: 1 Pages: 89-90
  • DOI: 10.1038/modpathol.2015.69
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Lower expression of CADM1 and higher expression of MAL in Merkel cell carcinomas are associated with Merkel cell polyomavirus infection and better prognosis. (2016)
  • Author(s): Iwasaki T, Matsushita M, Nonaka D, Nagata K, Kato M, Kuwamoto S, Murakami I, Hayashi K
  • Journal Title: Hum Pathol. Volume: 48 Pages: 1-8
  • DOI: 10.1016/j.humpath.2015.09.030
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A new in situ hybridization and immunohistochemistry with a novel antibody to detect small T-antigen expressions of Merkel cell polyomavirus (MCPyV). (2014)
  • Author(s): Matsushita M, Nonaka D, Iwasaki T, Kuwamoto S, Murakami I, Kato M, Nagata K, Kitamura Y, Hayashi K.
  • Journal Title: Diagn Pathol Volume: 9 Issue: 1 Pages: 65-65
  • DOI: 10.1186/1746-1596-9-65
  • Peer Reviewed / Open Access
• [Presentation] Ecology of merkel cell polyomavirus in healthy skin among individuals in an asian cohort shows close agreement with interleukin-1 loop model in langerhans cell histiocytosis. (2016)
  • Author(s): Murakami I, Nakashima J, Hashida Y, Daibata M, Matsushita M, Iwasaki T, Kuwamoto S, Kato M, Nagata K, Hayashi K, Oka T, Yoshino T, Imamura T, Morimoto A, Imashuku S, Gogusev J, Jaubert F.
  • Organizer: 32nd Annual Meeting of the Histiocyte Society
  • Place of Presentation: Dublin (Ireland)
  • Year and Date: 2016-10-17
  • Int'l Joint Research
• [Presentation] The relations of JAK-STAT signaling expressions to MCPyV-infection and outcome in Merkel cell carcinomas. (2016)
  • Author(s): Matsushita M, Iwasaki T, Nonaka D, Kuwamoto S, Nagata K, Kato M, Kitamura Y, Hayash K.
  • Organizer: XXXI International Congress of the International Academy of Pathology and 28th Congress of the European Society of Pathology
  • Place of Presentation: Cologne (Germany)
  • Year and Date: 2016-09-25
  • Int'l Joint Research
• [Presentation] Expression of a long non-coding RNA NEAT1 is significantly higher in MCPyV-positive Merkel cell carcinomas than MCPyV-negative ones. (2016)
  • Author(s): Akizuki G, Imamura K, Yamada T, Mizutani R, Matsushita M, Iwasaki T, Nonaka D, Kuwamoto S, Nagata K, Hayashi K, Akimitsu N.
  • Organizer: XXXI International Congress of the International Academy of Pathology and 28th Congress of the European Society of Pathology
  • Place of Presentation: Cologne (Germany)
  • Year and Date: 2016-09-25
  • Int'l Joint Research
• [Presentation] Biphasic production of immunoglobulin from Epstein-Barr virus reactivated lymphocytes in Graves' disease patients and controls. (2016)
  • Author(s): Nagata K, Kumata K, Nakayama Y, Satoh Y, Matsushita M, Kuwamoto S, Kato M, Sugihara H, Murakami I, Hayashi K.
  • Organizer: XXXI International Congress of the International Academy of Pathology and 28th Congress of the European Society of Pathology
  • Place of Presentation: Cologne (Germany)
  • Year and Date: 2016-09-25
  • Int'l Joint Research
• [Presentation] メルケル細胞癌におけるJAK-STAT経路活性化とMCPyVおよび予後との関係 (2016)
  • Author(s): 松下倫子、岩崎健、野中大輔、桑本聡史、長田佳子、加藤雅子、北村幸郷、林一彦
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター（宮城）
  • Year and Date: 2016-05-12
• [Presentation] メルケル細胞癌におけるHedgehog signal発現とMCPyV感染および予後との関連 (2016)
  • Author(s): 黒見晃行、松下倫子、岩崎健、野中大輔、桑本聡史、長田佳子、加藤雅子、北村幸郷、林一彦
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター（宮城）
  • Year and Date: 2016-05-12
• [Presentation] Activation-induced deaminase (AID) gene expressions in Merkel cell carcinomas.by immunohistochemical and molecular analysis (2015)
  • Author(s): Matsushita M, et al.
  • Organizer: 27th European Congress of Pathology
  • Place of Presentation: Belgrade (Serbia)
  • Year and Date: 2015-09-08
• [Presentation] Higher CADM1 expression and lower MAL expression in Merkel cell carcinomas (MCCs) are associated with MCPyV-negative MCCs and unfavorable outcome. (2015)
  • Author(s): Iwasaki T, Matsushita M, et al.
  • Organizer: 27th European Congress of Pathology
  • Place of Presentation: Belgrade (Serbia)
  • Year and Date: 2015-09-05 – 2015-09-09
• [Presentation] メルケル細胞癌の発癌における活性化誘導シチジンデアミナーゼ発現関与の検討 (2015)
  • Author(s): 松下倫子、他
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（愛知）
  • Year and Date: 2015-04-30