Molecular analysis for carcinogenesis surveillance in ulcerative colitis

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20855
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Center for Clinical and Biomedical Research, Sapporo Higashi Tokushukai Hospital
• Principal Investigator: Ishii Takahiro 医療法人徳洲会札幌東徳洲会病院医学研究所, がん生物研究部, 研究員 (50911989)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: TP53 / p53 / NGS / IHC

Outline of Final Research Achievements

We conducted a study using samples from 23 ulcerative colitis patients to evaluate the presence of abnormal cells and genetic mutations associated with colorectal cancer. We assessed histological atypia through HE staining and p53 immunostaining, and examined 9 driver genes associated with colorectal cancer. Our findings show that TP53 mutation detection using surgical resection material was more accurate than p53 immunostaining in detecting dysplasia and invasive cancer. We also found mutations in other genes such as KRAS, BRAF, APC, and FBXW7, in 37% of our participants. We are continuing to analyze more cases. However, some patients had positive p53 immunostaining in their biopsy specimens despite not having TP53 mutation, suggesting a possible uncertainty in histopathological assessment.

Free Research Field

がん生物研究

Academic Significance and Societal Importance of the Research Achievements

潰瘍性大腸炎(UC)の長期罹患例ではcolitic cancerの発生リスクが高く、その初期発生に関わるp53異常は一般にp53免疫染色を参考に判定されている。本研究により、発癌症例ではターゲットシーケンス解析によるTP53変異の陽性率が高く、内視鏡生検との一致率も高いことがわかった。UC患者の発癌サーベイランスには、より精度の高いTP53変異解析の導入を検討すべきである。今後、生検材料でのデータを前向きに集積することで、早期の診断と治療介入による予後改善が期待される。