Significance of p53-binding protein 1 as an in situ DNA damage marker for ulcerative colitis

Ulcerative colitis is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon. The extensive and persistent mucosal damage associated with ulcerative colitis (UC) can contribute to carcinogenesis, thereby underscoring the significant clinical interest in identifying an in situ marker. p53-binding protein (53BP1) is a DNA damage response (DDR) molecule that localizes at sites of double-strand breaks. Herein, we investigated the in situ DDR in UC by evaluating 53BP1 immunofluorescence. Our study revealed a significant increase in abnormal 53BP1 foci, defined as three or more foci and/or foci larger than 1 µm within the nucleus, in patients with UC compared to controls. Furthermore, the presence of abnormal 53BP1 foci in UC correlated with the severity of symptoms, endoscopic gradings, serological and histopathological inflammation. Of note, 53BP1 foci were observed in the colon mucosa of patients in remission, indicating that 53BP1 is a sensitive DDR marker. In addition, large 53BP1 foci, indicative of a severe DDR, were more prevalent in patients with colitic cancer than in controls. In conclusion, our findings suggest that 53BP1 may serve as a in situ marker reflecting the extent of the DDR in UC.