Abstract
To clarify the association between DNA damage response in tumor specimens of ductal resection margins and local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma. A retrospective analysis was conducted of 11 patients with positive ductal margins with carcinoma in situ. To evaluate the early DNA damage response, the nuclear staining pattern of p53-binding protein 1 (53BP1) was examined by immunofluorescence. Of the 11 tumor specimens of carcinoma in situ, 10 showed diffuse localization of 53BP1 in nuclei (53BP1 inactivation) and 4 showed discrete nuclear foci of 53BP1 (53BP1 activation); the apoptotic index was significantly decreased in the 7 tumor specimens with 53BP1 inactivation compared to the 4 with 53BP1 activation (median apoptotic index, 1% vs. 22%; p=0.003). Cumulative probability of local recurrence was significantly higher in patients with 53BP1 inactivation than in patients with 53BP1 activation (cumulative 5-year local recurrence rate, 60% vs. 0%; p=0.019). These data suggest that local recurrence is associated with 53BP1 inactivation and decreased apoptosis.
