Molecular characteristics of gastric caner in the elderly

• Project/Area Number: 16K08664
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Tokyo 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)
• Research Collaborator: MATSUDA Yoko ; NISHIMURA Makoto ; KUROIWA Koujiro ; KANAZAWA Nobuo
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 胃癌 / 高齢者 / マイクロサテライト不安定性 / KRAS遺伝子 / BRAF遺伝子 / CA19-9 / 遺伝子変化

Outline of Final Research Achievements

Gastric cancer (GC) in the elderly has shown clinicopathological characteristics such as higher proportion of microsatellite instability (MSI) and peculiar histologic types (solid-type poorly differentiated and papillary adenocarcinomas). Although GC in the elderly showed lower proportion of KRAS and BRAS mutation, GC with KRAS mutation was associated with MSI and specific histology such as moderately differentiated tubular adenocarcinoma and mucinous carcinoma. These results could contribute the elucidation of mechanism of carcinogenesis of GC in the elderly, and could be a basis for exploring development and adaptation of molecular targeted drugs corresponding to their molecular changes. Furthermore, if pathological features of GC in the elderly are to some extent clarified, it could also contribute to the development of a treatment for GC in the elderly.

Academic Significance and Societal Importance of the Research Achievements

高齢者胃癌の特徴として、マイクロサテライト不安定性（以下、MSI）が高率であること、MSIを示す組織型は充実型低分化腺癌、乳頭腺癌であることが明らかになった。また分子病理学的には、KRAS・BRAF遺伝子変異率は低いものの、KRAS遺伝子変異が中分化管状腺癌や粘液癌などの特定の組織型との関連がみられた。これら高齢者癌の臨床病学的、分子病理学的特徴は、高齢者胃癌の発赤機序の解明に寄与し、その変化に対応する分子標的薬の開発・適応を模索する基盤となりうる。さらに高齢者胃癌の病理学的特徴が明らかになれば、特定の遺伝子変異を示す胃癌の治療法の開発などにも貢献できる。

Research Products

• [Int'l Joint Research] Maastricht University Medical Center/Leiden University Medical Center(オランダ)
• [Int'l Joint Research] University of Leeds(英国)
• [Int'l Joint Research] Duke-NUS Medical School(シンガポール)
• [Int'l Joint Research] Maastricht University(オランダ)
• [Int'l Joint Research] University of Leeds(United Kingdom)
• [Int'l Joint Research] Duke-NUS Medical School(Singapore)
• [Int'l Joint Research] Maastricht University(オランダ)
• [Journal Article] Solid-type poorly differentiated adenocarcinoma of the stomach: clinicopathological and molecular characteristics and histogenesis (2019)
  • Author(s): Arai Tomio、Matsuda Yoko、Aida Junko、Takubo Kaiyo、Ishiwata Toshiyuki
  • Journal Title: Gastric Cancer Volume: 22 Issue: 2 Pages: 314-322
  • DOI: 10.1007/s10120-018-0862-6
  • NAID: 40021832716
  • Peer Reviewed
• [Journal Article] KRAS status is related to histological phenotype in gastric cancer: results from a large multicentre study (2019)
  • 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: 印刷中
  • NAID: 40022051098
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] Identification of a high-risk subtype of intestinal-type Japanese gastric cancer by quantitative measurement of the luminal tumor proportion (2018)
  • Author(s): Aoyama Toru、Hutchins Gordon、Arai Tomio、Sakamaki Kentaro、Miyagi Yohei、Tsuburaya Akira、Ogata Takashi、Oshima Takashi、Earle Sophie、Yoshikawa Takaki、Grabsch Heike I.
  • Journal Title: Cancer Medicine Volume: 7 Issue: 10 Pages: 4914-4923
  • DOI: 10.1002/cam4.1744
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 高齢者がんの臨床病理学的特徴 (2018)
  • Author(s): 新井冨生、松田陽子、相田順子、田久保海誉、石渡俊行
  • Journal Title: 腫瘍内科 Volume: 21 Pages: 212-220
  • NAID: 10027914023
• [Journal Article] Frequent Coamplification of Receptor Tyrosine Kinase and Downstream Signaling Genes in Japanese Primary Gastric Cancer and Conversion in Matched Lymph Node Metastasis (2018)
  • Author(s): Silva ANS, Coffa J, Menon, HewittLC, Das K, Miyagi Y, Bottomley D, Slaney H, Aoyama T, Mueller W, Arai T, Tan IB, Deng N, Chan XB, Tan P, Tsuburaya A, Sakamaki K, Hayden JD, Yoshikawa T, Zondervan I, Savola S, Grabsch HI
  • Journal Title: Annals of Surgery Volume: 267 Issue: 1 Pages: 114-121
  • DOI: 10.1097/sla.0000000000002042
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Carbohydrate Antigen 19-9-Positive Gastric Adenocarcinoma: Autopsy Findings and Review of the Literature (2017)
  • Author(s): Wang Tan、Matsuda Yoko、Seki Atsuko、Nonaka Keisuke、Kakizaki Mototsune、Kaneda Daita、Takahashi-Fujigasaki Junko、Murayama Shigeo、Arai Tomio
  • Journal Title: Case Reports in Gastroenterology Volume: 11 Issue: 3 Pages: 545-553
  • DOI: 10.1159/000479223
  • Peer Reviewed / Open Access
• [Journal Article] Association of Macrophage Capping Protein (CAPG) Arg335His Polymorphism and Cancer Susceptibility in the Elderly Japanese (2017)
  • Author(s): Dechamethakun Sariya、Sato Noriko、Ikeda Shinobu、Sawabe Motoji、Mori Seijiro、Yamada Yoshiji、Tanaka Masashi、Muramatsu Masaaki、Arai Tomio
  • Journal Title: Journal of Gerontology & Geriatric Research Volume: 06 Issue: 02 Pages: 417-417
  • DOI: 10.4172/2167-7182.1000417
  • Peer Reviewed / Open Access
• [Journal Article] Frequent coamplification of receptor tyrosine kinase and downstream signaling genes in Japanese primary gastric cancer and conversion in matched lymph node metastasis (2017)
  • Author(s): Silva ANS, Coffa J, Menon V, Hewitt LC, Das K, Miyagi Y, Bottomley D, Slaney H, Aoyama T, Mueller W, Arai T, Tan IB, Deng N, Chan XB, Tan P, Tsuburaya A, Sakamaki K, Hayden JD, Yoshikawa T, Zondervan I, Savola S, Grabsch HI
  • Journal Title: Ann Surg Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Association of macrophage capping protein (CAPG) Arg335His polymorphism and cancer susceptibility in the elderly Japanese (2017)
  • Author(s): Dechamethakun S, Sato N, Ikeda S, Sawabe M, Mori S, Yamada Y, Tanaka M, Muramatsu M, Arai T
  • Journal Title: J Gerontol Geriatr Res Volume: 印刷中
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [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
  • Int'l Joint Research / Invited
• [Presentation] Aggressive features of gastrointestinal melanoma as compared to skin melanoma (2018)
  • Author(s): Akiyama M, Matsuda Y, Arai T, Saeki H
  • Organizer: Annual Meeting of the American Association of Cancer Research 2018
  • Int'l Joint Research
• [Presentation] Clinicopathological diversity of solid-type poorly differentiated adenocarcinoma of the stomach (2018)
  • Author(s): Arai T, Matsuda Y, Wang T, Aida J, Takubo K
  • Organizer: XXXII International Academy of Pathology
  • Int'l Joint Research
• [Presentation] 消化管癌と遺伝子変異の関連について：病理学的観点から (2018)
  • Author(s): 新井冨生
  • Organizer: 第77回日本癌学会学術総会
  • Invited
• [Presentation] EUS-FNAで診断し得た胃の神経鞘腫の一例 (2018)
  • Author(s): 児島宏哉、白幡浩人、木曽有里、浜島裕理、江坂四季音、木下真由美、今泉雅之、鈴木明美、松田陽子、新井冨生
  • Organizer: 第59回日本臨床細胞学会総会春期大会
• [Presentation] ALDH2遺伝子多型と発がんリスクとの関連解析 (2018)
  • Author(s): 新井冨生、田中雅嗣
  • Organizer: 第65回日本臨床検査医学会学術集会
• [Presentation] Pathological diagnosis of adenocarcinoma of the esophagogastric junction (2018)
  • Author(s): Arai T
  • Organizer: 第90回日本胃癌学会総会
  • Invited
• [Presentation] Mutaion of KRAS and BRAF genes and microsatellite status in gastric cancer in the elderly (2018)
  • Author(s): Wang T, Matsuda Y, Seki A, Nonaka K, Kakizaki M, Aida J, Takubo K, Ishiwata T, Grabsch HI, Arai T
  • Organizer: 第90回日本胃癌学会総会
• [Presentation] 大腸髄様癌とそれに関連するマイクロサテライト不安定性を示す大腸癌の病理学的特徴 (2017)
  • Author(s): 新井冨生，松田陽子，関 敦子，相田順子，田久保海誉．石渡俊行
  • Organizer: 第63回日本病理学会秋期特別総会
• [Presentation] Pathological diagnosis of esophageal adenocarcinoma (EAC): The Japanese viewpoint (2017)
  • Author(s): 新井冨生
  • Organizer: 第71回日本食道学会総会
  • Invited
• [Presentation] 臓器別シンポジウム13「それぞれの癌」：診断・治療の現状と展望‐食道‐ 食道扁平上皮癌・腺癌の病理診断：最近の話題 (2017)
  • Author(s): 新井冨生，大倉康男，八尾隆史，根本哲生，河内 洋，眞能正幸，向所賢一，渡邉 玄，柳澤昭夫
  • Organizer: 第55回日本癌治療学会学術集会
  • Invited
• [Presentation] KRAS and BRAF mutation and microsatellite instability status in gastric cancer in the elderly (2016)
  • Author(s): Arai T, Wang T, Matsuda Y, Seki A, Nonaka K, Kakizaki M, Aida J, Takubo K, Ishiwata T
  • Organizer: XXXI International Congress of the International Academy of Pathology and 28th Congress of the European Society of Pathology
  • Place of Presentation: Koelnmesse, Koeln, Germany
  • Year and Date: 2016-09-27
  • Int'l Joint Research
• [Presentation] Histopathological characteristics of MSI cancers in the upper and lower GI tract?; do they have anything in common? (2016)
  • Author(s): Arai T
  • Organizer: International Symposium on improving outcomes in patients with gastrointestinal malignancies requires an international multidisciplinary approach
  • Place of Presentation: Maastricht University, the Netherlands
  • Year and Date: 2016-07-08
  • Int'l Joint Research / Invited
• [Book] 図解病理解剖ガイド (2018)
  • Author(s): 新井冨生
  • Total Pages: 176
  • Publisher: 文光堂
  • ISBN: 9784830604805