Attempts to elucidate the pathogenesis of PCCRC

• Project/Area Number: 19K17493
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Hiroshima University
• Principal Investigator: Ninomiya Yuki 広島大学, 病院(医), 専門研究員 (40838736)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2020: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2019: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
• Keywords: PCCRC / dMMR / PIK3CA / 癌ゲノム解析 / missed cancer

Outline of Research at the Start

現在まで当院での約1900症例の大腸がん治療後サーベイランス症例の集積の結果，34例のPost-colonoscopy colorectal cancer (PCCRC)を同定しており，近位結腸の頻度が高く，扁平隆起性病変が多かった。初年度にPCCRCの内視鏡拡大所見や病理組織学的所見の特徴の同定，gDNAの抽出，MSI関連の免疫染色，ベセスダ5領域のフラグメント解析によるMSI解析，大腸癌関連遺伝子のdeep sequence，DNAメチル化マーカーの検討，腫瘍の悪性度の評価を行い，次年度に多施設での上記結果のValidationを行う予定である。

Outline of Final Research Achievements

This study aimed to determine the clinicopathological, biological, and genomic characteristics of post-colonoscopy CRCs (PCCRCs). 32 patients with 34 PCCRCs were enrolled. The overall PCCRC-5y rate, rate of intramucosal (Tis) lesions, and rate of T1 or more deeply invasive cancers were 3.7% , 3.9%, and 3.6%, respectively. 21% exhibited deficient MMRs (dMMRs), comprising 4 with T2 or more deeply invasive cancers and 5 whose lesions were in the proximal colon. PIK3CA had mutated in 5 of 6 T2 or more deeply invasive cancers, of which, 4 were located in the proximal colon. 2 patients with dMMRs and BRAFV600E mutations had poor prognoses. All superficial Tis and T1 PCCRCs were detected <24 months after the negative colonoscopies. They were distributed throughout the colon and rectum. This study suggested PCCRCs may be invasive cancers in the proximal colon that exhibit dMMRs and/or PIK3CA mutations or missed early CRCs especially superficial lesions.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、大腸内視鏡における大腸癌のサーベイランス方法に大いに寄与する可能性がある。多発大腸腫瘍では最初の腫瘍での臨床病理学的所見やゲノムプロファイリングは異時性病変のそれと似通っているため、最初の腫瘍でこれらの所見を検討する事によって、サーベイランス間隔を短縮して行えると考えられる。またサーベイランス間隔が比較的長期間にも関わらずPCCRCが出現しない症例を検討することによって、サーベイランス間隔を延長する事ができる。このような効果は早期段階で大腸癌の治療を行う事によって患者の生命予後に寄与するだけでなく、不必要な検査・治療を省略し医療経済的な観点からも有用である。

Research Products

• [Journal Article] Clinical Features and Genomic Characterization of Post-Colonoscopy Colorectal Cancer (2020)
  • Author(s): Tanaka Hidenori、Urabe Yuji、Oka Shiro、Shimohara Yasutsugu、Nishimura Tomoyuki、Inagaki Katsuaki、Okamoto Yuki、Matsumoto Kenta、Yamashita Ken、Sumimoto Kyoku、Ninomiya Yuki、Yuge Ryo、Tanaka Shinji、Chayama Kazuaki
  • Journal Title: Clinical and Translational Gastroenterology Volume: 11 Issue: 10 Pages: e00246-e00246
  • DOI: 10.14309/ctg.0000000000000246
  • Peer Reviewed / Open Access
• [Presentation] post-colonoscopy colorectal cancer (PCCRC)の臨床的・遺伝学的特徴 (2020)
  • Author(s): 卜部祐司 田中 信治 茶山 一彰
  • Organizer: 第100回日本内視鏡学会(JDDW2020)
• [Presentation] LINICAL FEATURES AND GENOMIC CHARACTERIZATION OF POST-COLONOSCOPY COLORECTAL CANCER (2020)
  • Author(s): Tanaka H., Urabe Y., Oka S., Shimohara Y., Nishimura T., Inagaki K., Okamoto Y., Matsumoto K., Yamashita K., Sumimoto K., Ninomiya Y., Yuge R., Tanaka S., Chayama K.
  • Organizer: United European Gastroenterology Week 2020
  • Int'l Joint Research