Analysis on the differences of tumorigenesis between MCPyV-positive and -negative Merkel cell carcinomas and its application to therapy

2016 Fiscal Year Annual Research Report

• Project/Area Number: 26460433
• Research Institution: Tottori University
• Principal Investigator: 林 一彦 鳥取大学, 医学部, 教授 (30180962)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: メルケル細胞癌 / ポリオーマウイルス

Outline of Annual Research Achievements

１．メルケル細胞癌(MCC)における接着因子CADM1の低発現とMALの高発現が、Merkel cell polyomavirus(MCPyV)の感染したこの癌の群でよく見られ、良好な予後とも有意に相関することを報告した(Iwasaki et al., Hum Pathol 2016)。
２．MCC診断の一般的指標となるCytokeratin 20発現が陰性となるMCC群ではMCPyVの感染が稀であることを確認し、報告した(Iwasaki et. al., Mod Pathol. 2016)。」
３．遺伝子変異原性酵素Activation-induced cytidine deaminase(AID)の発現量と次世代シークエンサー解析(NGS)による遺伝子変異頻度と遺伝子変異プロファイルの両群での比較検討：
ウイルス・微生物の感染・炎症で誘導される変異原性酵素AIDとその調節因子のMCCでの発現をMCPyV(+)群と MCPyV(-)群とで比較検討した結果、ウイルス感染で誘導されるNF-kB(AID誘導因子）の発現がMCPyV(+)MCC群で有意に高いにもかかわらず, AID発現はMCPyV(-)MCC群の方が有意に高いことが判明した。この事実は、NGSによる一部のがん遺伝子のシークエンス解析で得られたMCPyV(-)ＭＣＣ群の方が遺伝子変異の頻度が高い結果と合致していた。紫外線によるＣから Tへの変異が両群で高頻度に見られた（投稿中）。

Research Products

• [Int'l Joint Research] Department of Histopathology,/the Christie NHS Foundation Trust,/Manchester(United Kingdom)
  • Country Name: United Kingdom
  • Counterpart Institution: Department of Histopathology,/the Christie NHS Foundation Trust,/Manchester
• [Journal Article] Comment on 'Cytokeratin 20-negative Merkel cell carcinoma is infrequently associated with the Merkel cell polyomavirus' (2016)
  • Author(s): T Iwasaki, M Matsushita, D Nonaka, I Murakami, K. Hayashi
  • Journal Title: Mod Pathol. Volume: 29 Pages: 89-90
  • DOI: 10.1038/modpathol.2015.69.
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [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): Takeshi Iwasaki, Michiko Matsushita, Daisuke Nonaka, Keiko Nagata, Masako Kato, Satoshi Kuwamoto, Ichiro Murakami, Kazuhiko Hayashi
  • Journal Title: Hum Pathol Volume: 48 Pages: 1-8
  • DOI: 10.1016/j.humpath
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Thyrotropin receptor antibody (TRAb)-IgM levels are markedly higher than TRAb-IgG levels in Graves’ disease patients and controls, and TRAb-IgM production is related to EBV reactivation. (2016)
  • Author(s): K Kumata, K Nagata, M Matsushita, S Kuwamoto, M Kato, I Murakami, S Fukata, K Hayashi
  • Journal Title: Viral Immunol. Volume: 29 Pages: 459-463
  • DOI: 10.1089/vim.2016.0043
  • Peer Reviewed
• [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): Gen Akizuki, Katsutoshi Imamura, Toshimichi Yamada, Aiko Sato, Rena Mizutani, Michiko Matsushita, Takeshi Iwasaki, Daisuke Nonaka, Satoshi Kuwamoto, Keiko Nagata, Masako Kato, Nobuyoshi Akimitsu, Kazuhiko Hayashi
  • Organizer: European Congress of Patholgy
  • Place of Presentation: Cologne, Germany
  • Year and Date: 2016-09-25 – 2016-09-29
  • Int'l Joint Research
• [Presentation] The relations of JAK-STAT signaling expressions to MCPyV-infection and outcome in Merkel cell carcinoma. (2016)
  • Author(s): Michiko Matsushita, Takeshi Iwasaki, Daisuke Nonaka, Satoshi Kuwamoto, Keiko Nagata, Masako Kato, Yukisato Kitamura, Kazuhiko Hayashi
  • Organizer: 28th European Congress of Patholgy
  • Place of Presentation: Cologne, Germany
  • Year and Date: 2016-09-25 – 2016-09-29
  • Int'l Joint Research
• [Presentation] Biphasic production of immunoglobulin from EBV reactivated PBMCs in Graves’ disease patients and controls (2016)
  • Author(s): Keiko Nagata, Keisuke Kumata, Yuji Nakayama, Yukio Satoh, Michiko Matsushita, Ichiro Murakami, Satoshi Kuwamoto, Masako Kato, Hirotsugu Sugihara, Kazuhiko Hayashi
  • Organizer: 28th European Congress of Patholgy
  • Place of Presentation: Cologne, Germany
  • Year and Date: 2016-09-25 – 2016-09-29
  • 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回病理学会総会
  • Place of Presentation: 仙台国際センター、（宮城県仙台市）
  • Year and Date: 2016-05-12 – 2016-05-14
• [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回病理学会総会
  • Place of Presentation: 仙台国際センター、（宮城県仙台市）
  • Year and Date: 2016-05-12 – 2016-05-14