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Research for therapeutic strategies based on molecular and pathological characteristics of gastric cancer in the elderly

Research Project

Project/Area Number 19K07428
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionTokyo Metropolitan Geriatric Hospital and Institute of Gerontology

Principal Investigator

Arai Tomio  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (20232019)

Co-Investigator(Kenkyū-buntansha) 松田 陽子  香川大学, 医学部, 教授 (20363187)
Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords胃癌 / 高齢者 / 乳頭腺癌 / マイクロサテライト不安定性 / PD-L1 / 免疫チェックポイント阻害剤 / 印環細胞癌 / 低分化腺癌 / 早期胃癌 / 内視鏡切除 / 免疫チェックポイント / 病理解剖 / CA19-9 / 凝固異常 / 免疫組織化学 / マイクロサテライト
Outline of Research at the Start

胃癌は加齢とともに発生率が急増する代表的ながんであり、病理学的に高齢者胃癌は若年者とは異なる病態を示す。本研究では高齢者で相対的に急増するマイクロサテライト不安定性経路による胃癌に焦点をあて、高齢者胃癌の発癌機序、臨床病理像、遺伝子異常を明らかにするとともに、最近注目されている免疫チェックポイント阻害剤の高齢者胃癌への適応について検討する。また、高齢者では悪性腫瘍による凝固系異常が発症しやすいので、その合併症対策も含め新しい治療戦略に寄与することを目的とする。

Outline of Final Research Achievements

We investigated 336 cases of gastric cancer to clarify clinicopathological characteristics of patients aged 80 years or older. Characteristics observed in the elderly with gastric cancer, such as antral location, elevated gross type, differentiated type, increased number of multiple cancers, and low lymph node metastasis, tended to be more evident in those aged 80 years or older. In addition, 40 cases were analyzed to clarify the molecular pathological characteristics of papillary adenocarcinoma among aged patients with gastric cancer and the indications for immune checkpoint inhibitors. Microsatellite instability (MSI) was observed in 43% of papillary adenocarcinomas. In papillary adenocarcinomas with MSI, there was an association with female gender, lower-stage origin, the presence of mixed poorly differentiated adenocarcinoma components, and the proportion of early-stage cancers. The positive rate of PD-L1 expression was 63%, with a higher positive rate in MSI cases.

Academic Significance and Societal Importance of the Research Achievements

胃癌発生は減少傾向にあるとは言え,高齢者においてはまだ重要な疾患である.高齢者胃癌の臨床病理学的および分子病理学的特徴を明らかにすることにより,高齢者胃癌の病態および病因の解明に寄与することができる点に学術的意義がある.また社会的には,学術的なエビデンスに基づき,高齢者胃癌の病態に対応する低侵襲な治療法の選択肢を提示することができる.

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (29 results)

All 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (4 results) Journal Article (14 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 14 results,  Open Access: 5 results) Presentation (10 results) (of which Int'l Joint Research: 8 results,  Invited: 6 results) Remarks (1 results)

  • [Int'l Joint Research] Maastrichit University(オランダ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] University of Leeds(英国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Maastricht University(オランダ)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Leeds University(英国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Clinicopathological and molecular characteristics of gastric papillary adenocarcinoma2023

    • Author(s)
      Arai Tomio、Komatsu Akiko、Kanazawa Nobuo、Nonaka Keisuke、Ishiwata Toshiyuki
    • Journal Title

      Pathology International

      Volume: 73 Issue: 8 Pages: 358-366

    • DOI

      10.1111/pin.13345

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] tumor-infiltrating lymphocytes (TILs)2022

    • Author(s)
      新井冨生
    • Journal Title

      胃と腸

      Volume: 57 Pages: 724-724

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Crohn's-like lymphoid reaction2022

    • Author(s)
      新井冨生
    • Journal Title

      胃と腸

      Volume: 57 Pages: 725-725

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] 今月の主題 胃上皮性腫瘍-組織分類・内視鏡診断の新展開 主題研究 印環細胞癌の組織分類における最新知見2021

    • Author(s)
      新井冨生
    • Journal Title

      胃と腸

      Volume: 56 Issue: 10 Pages: 1356-1366

    • DOI

      10.11477/mf.1403202562

    • ISSN
      0536-2180, 1882-1219
    • Year and Date
      2021-09-25
    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prediction model for gastric cancer with DNA mismatch repair deficiency2021

    • Author(s)
      Suzuki O, Yamaguchi T, Fukuchi M, Mochiki E, Arai T, Akagi K, Ishida H
    • Journal Title

      Anticancer Res

      Volume: 41 Issue: 2 Pages: 975-982

    • DOI

      10.21873/anticanres.14851

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] D-amino acid oxidase (DAO) rare genetic missense variant p.Pro103Leu and gastric cancer2021

    • Author(s)
      Zong Yuan, Tanaka Masashi, Muramatsu Masaaki, Arai Tomio
    • Journal Title

      Molecular and Clinical Oncology

      Volume: 14 Issue: 3 Pages: 58-58

    • DOI

      10.3892/mco.2021.2220

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comprehensive analysis of DNA mismatch repair-deficient gastric cancer in a Japanese hospital-based population2021

    • Author(s)
      Ito Tetsuya, Suzuki Okihide, Kamae Nao, Tamaru Jun-ichi, Arai Tomio, Yamaguchi Tatsuro, Akagi Kiwamu, Eguchi Hidetaka, Okazaki Yasushi, Mochiki Erito, Ishida Hideyuki
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: - Issue: 6 Pages: 886-894

    • DOI

      10.1093/jjco/hyab026

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mucin expression in gastric- and gastro-oesophageal signet-ring cell cancer: results from a comprehensive literature review and a large cohort study of Caucasian and Asian gastric cancer2020

    • Author(s)
      Kerckhoffs K.G.P., Liu D.H.W., Saragoni L., van der Post R.S., Langer R., Bencivenga M., Iglesias M., Gallo G., Hewitt L.C, 、Fazzi G.E., Vos A.M., Renaud F., Yoshikawa T., Oshima T., Tomezzoli A., de Manzoni G., Arai T., Kushima R., Carneiro F., Grabsch H.I.
    • Journal Title

      Gastric Cancer

      Volume: 23 Issue: 5 Pages: 765-779

    • DOI

      10.1007/s10120-020-01086-0

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 高齢者早期胃癌の病理学的特徴2020

    • Author(s)
      新井冨生,野中敬介,小松明子,井下尚子,相田順子,石渡俊行,松川美保,西村 誠,上垣佐登子,吉田孝司,金澤伸郎
    • Journal Title

      胃と腸

      Volume: 55 Pages: 1449-1460

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Do we need special viewpoints for intraoperative frozen section diagnosis?2020

    • Author(s)
      Arai Tomio
    • Journal Title

      Virchows Archiv

      Volume: 477 Issue: 5 Pages: 761-762

    • DOI

      10.1007/s00428-020-02862-0

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinicopathological characteristics of gastric cancer with carbohydrate antigen 19-9 expression occurring in elderly individuals: an autopsy study.2020

    • Author(s)
      145.Wang T, Matsuda Y, Nonaka K, Kakizaki M, Ishiwata T, Kanazawa N, Uegaki S, Muramatsu M, Sawabe M, Mori S, Kitagawa M, Arai T.
    • Journal Title

      Pathology International

      Volume: 70 Issue: 2 Pages: 92-100

    • DOI

      10.1111/pin.12882

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comprehensive biomarker analyses identifies HER2, EGFR, MET RNA expression and thymidylate synthase 5'UTR SNP as predictors of benefit from S-1 adjuvant chemotherapy in Japanese patients with stage II/III gastric cancer2019

    • Author(s)
      Yoshikawa T, Aoyama T, Sakamaki K, Oshima T, Lin J, Zhang S, Sapari NS, Soong R, Tan I, Chan XB, Bottomley D, Hewitt LC, Arai T, Teh BT, Epstein D, Ogata T, Kameda Y, Miyagi Y, Tsuburaya A, Morita S, Grabsch HI, Tan P
    • Journal Title

      Journal of Cancer

      Volume: 10 Issue: 21 Pages: 5130-5138

    • DOI

      10.7150/jca.34741

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] KRAS status is related to histological phenotype in gastric cancer: results from a large multicentre study2019

    • Author(s)
      Hewitt LC, Saito Y, Wang T, Matsuda Y, Oosting J, Silva ANS, Slaney HL, Melotte V, Hutchins G, Tan P, Yoshikawa T, Arai T, Grabsch HI
    • Journal Title

      Gastric Cancer

      Volume: 22 Issue: 6 Pages: 1193

    • DOI

      10.1007/s10120-019-00972-6

    • NAID

      40022051098

    • URL

      https://pure.teikyo.jp/en/publications/5a6a37fd-f893-42c4-a750-b86c9cf45f6a

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Where does signet-ring cell carcinoma come from and where does it go?2019

    • Author(s)
      Arai T
    • Journal Title

      Gastric Cancer

      Volume: 印刷中 Issue: 4 Pages: 651-652

    • DOI

      10.1007/s10120-019-00960-w

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] Comparison between JGCA and WHO classification of signet ring cell and poorly cohesive carcinoma. In Pathology session “Refining poorly cohesive”2023

    • Author(s)
      Arai Tomio
    • Organizer
      International Gastric Cancer Congress (IGCC) 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Clinicopathological and definition of undifferentiated-type carcinoma: the Japanese pathologist’s view2023

    • Author(s)
      Arai Tomio
    • Organizer
      The 10th Korean International Gastric Cancer Association (KINGCA) WEEK 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Age-related increase of proportion of microsatellite instability in gastric, colorectal, and endometrial carcinomas2023

    • Author(s)
      Arai Tomio、Komatsu Akiko、Nagasaka Takuya、Nonaka Keisuke、Ishiwata Toshiyuki
    • Organizer
      International Academy of Geriatrics and Gerontology (IAGG) Asia/Oceania Regional Congress 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 高齢者におけるMSI-H胃癌の臨床病理学的特徴2022

    • Author(s)
      新井冨生
    • Organizer
      第94回日本胃癌学会総会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Classification of undifferentiated cancer; poorly cohesive, signet ring cell, and poorly differentiated adenocarcinoma: Japanese Pathologist’s view2021

    • Author(s)
      Tomio Arai
    • Organizer
      Korean International Gastric Cancer (KINGCA) week 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Clinicopathological and molecular characteristics of poorly differentiated adenocarcinoma of the stomach2020

    • Author(s)
      Arai T, Inoshita N, Nonaka K, Aida J, Ishiwata T
    • Organizer
      32nd Congress of the European Society of Pathology and XXXIII International Congress of the International Academy of Pathology
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] マイクロサテライト不安定性を示す腫瘍の病理診断2020

    • Author(s)
      新井冨生
    • Organizer
      第66回日本病理学会秋期特別総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Worshop: signet-ring cell carcinoma. Pure SRC and poorly cohesive tumours: do they have a transitional relationship?2019

    • Author(s)
      Arai T
    • Organizer
      The 13th International Gastric Cancer Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Clinicopathological diversity of solid-type poorly differentiated adenocarcinoma of the stomach2019

    • Author(s)
      Arai T, Matsuda Y, Wang T, Aida J, Takubo K
    • Organizer
      The 13th International Gastric Cancer Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] KRAS mutation, not KRAS amplification is related to histological phenotype in gastric cancer2019

    • Author(s)
      Hewitt L, Saito Y, Wang T, Matsuda Y, Oosting J, Silva A, Slaney H, Melotte V, Hutchins G, Tan P, Yoshikaw T, Arai T, Grabsch H
    • Organizer
      The 13th International Gastric Cancer Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Remarks] 地方独立行政法人東京都健康長寿医療センター研究所老年病理学研究チーム高齢者がん研究グループ

    • URL

      https://ttaggg-rtgp.org/

    • Related Report
      2023 Annual Research Report

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Published: 2019-04-18   Modified: 2025-01-30  

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