Establishment of a new methodology to distinguish between benign and malignant lesions in bile duct biopsy specimens based on an early repair mechanism for DNA double-strand breaks

• Project/Area Number: 17K10691
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Niigata University
• Principal Investigator: Ishikawa Hirosuke 新潟大学, 医歯学総合研究科, 客員研究員 (80769399)
• Co-Investigator(Kenkyū-buntansha): 小林 隆 新潟大学, 医歯学系, 准教授 (40464010) ; 若井 俊文 新潟大学, 医歯学系, 教授 (50372470) ; 坂田 純 新潟大学, 医歯学系, 講師 (70447605)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: γH2AX / 53BP1 / 胆管癌 / 生検 / 診断 / 蛍光二重免疫染色 / 免疫組織化学 / 胆管生検試料

Outline of Final Research Achievements

It is sometimes difficult to distinguish between malignant and benign lesions in bile duct biopsy specimens because of the tiny sample size and the influence of inflammatory change. Here, we have shown that the laveling index of γH2AX-positive cells with a focal staining by immunohistochemistry might be a useful biomarker to discriminate between benign and malignant lesions in bile duct biopsy specimens. In addition, we have revealed by double-label immunofluorescence that the percentage of tumor cells with γH2AX-positive foci which colocalized with 53BP1 was useful to discriminate between malignant and benign lesions in bile duct biopsy specimens.

Academic Significance and Societal Importance of the Research Achievements

胆管上皮の組織生検材料は、サイズが非常に小さいことや、胆管炎による影響により、組織学的な良悪性判定が困難となる場合がある。我々は、胆管上皮の組織生検材料に対して免疫組織化学および二重蛍光免疫組織染色を行い、癌・非癌を鑑別するための新たな病理組織学的評価方法の一つを提示できたと考える。

Research Products

• [Presentation] 胆管生検組織標本の良・悪性判定にγH2AX発現が有用である (2018)
  • Author(s): 石川 博補, 廣瀬 雄己, 永橋 昌幸, 坂田 純, 相馬 大輝, 安藤 拓也, 油座 築, 堅田 朋大, 三浦 宏平, 滝沢 一泰, 小林 隆, 田島 陽介, 市川 寛, 羽入 隆晃, 島田 能史, 亀山 仁史, 若井 俊文
  • Organizer: 日本外科学会定期学術集会
• [Presentation] 胆管生検で採取した正常上皮・炎症上皮・癌組織におけるDNA二本鎖切断のマーカーであるγH2AX発現の検討 (2018)
  • Author(s): 廣瀬 雄己, 坂田 純, 安藤 拓也, 油座 築, 堅田 朋大, 三浦 宏平, 滝沢 一泰, 永橋 昌幸, 小林 隆, 若井 俊文
  • Organizer: 日本消化器外科学会総会
• [Presentation] γH2AX expression discriminates between benign and malignant biliary tract biopsy specimens (2017)
  • Author(s): Yuki HIROSE, Masayuki NAGAHASHI, Hirosuke ISHIKAWA, Kizuki YUZA, Kohei MIURA, Hiroshi ICHIKAWA, Yoshifumi SHIMADA, Hitoshi KAMEYAMA, Jun SAKATA, Takashi KOBAYASHI, Toshifumi WAKAI
  • Organizer: Annual Academic Surgical Congress
  • Int'l Joint Research