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Molecular pathological characteristics in tamoxifen-related endometrial cancer

Research Project

Project/Area Number 20K17594
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionJuntendo University

Principal Investigator

Uomori Toshitaka  順天堂大学, 医学部, 准教授 (50529352)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords乳癌 / タモキシフェン / 内分泌療法 / 子宮体癌
Outline of Research at the Start

乳癌術後には再発予防を目的として内分泌療法が行われるが、代表的薬剤であるタモキシフェンの副作用として子宮体癌の発生が知られている。しかし未だに有効な予測・予防方法が確立していない。従って本薬剤を服用する患者は何年もの間不安を抱きながら頻回の婦人科検診や組織診を余儀なくされている。一方で、最近タモキシフェンの術後推奨服用期間が10年へと延長され、今後本疾患の発生が増加することは必至である。
本研究ではマイクロサテライト不安定性に注目し、なぜタモキシフェンにより子宮体癌が誘発されるのかを明らかにし、本疾患の予測と予防方法の確立を目指す。

Outline of Final Research Achievements

First, we investigated the MSI status of TAM-induced endometrial carcinomas and found that MSI-high tumors were more frequent than sporadic endometrial carcinomas. Furthermore, we confirmed that MMR protein expression was absent in MSI-high tumors. Next, surgical specimens from both groups were analyzed for genetic mutations in the cancer area using an oncogene panel on a next-generation sequencer. As a result, we identified several genes with significantly higher CNV in TAM-induced endometrial cancers. On the other hand, no differences were observed in the expression of proteins corresponding to these genes. We believe that our data may provide useful information for the interpretation of data obtained in future studies of TAM-induced endometrial cancer.

Academic Significance and Societal Importance of the Research Achievements

我々はまずTAM誘発子宮体癌においてMSI-highの腫瘍の頻度が有意に高いことを明らかにした。さらに次世代シークエンサーを用いて解析によりTAM誘発子宮体癌においてCNVの有意に高い複数の遺伝子を同定した。本研究の成果は、今後同様にTAM誘発子宮体癌の研究を行っていく上で、研究計画の立案やデータ解釈の際に非常に有用な情報になり得ると考えている。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (1 results)

All 2022

All Presentation (1 results)

  • [Presentation] Microsatellite instability in tamoxifen-related endometrial cancer2022

    • Author(s)
      Harumi Saeki, Yoshiya Horimoto, Tsuyoshi Saito, Takashi Yao
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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