Alteration of p53-binding protein 1 expression as a risk factor for local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma

本研究旨在阐明53BP1在肝外胆管癌切除术边缘肿瘤标本中介导的早期DNA损伤反应，并阐明其对110例肝外胆管癌切除术患者中临床上明显的胆管残端局部复发的预测价值。导管边缘状态是局部复发的唯一独立危险因素（P= 0.05）。001)。在导管边缘阴性、原位癌阳性和浸润癌阳性的患者中，5年累积局部复发概率分别为10%、40%和100% （P< 0.05）。001)。14例原位癌中，10例53BP1在细胞核中弥漫性定位（53BP1失活），4例53BP1在细胞核中离散灶（53BP1激活）。53BP1失活的肿瘤标本的凋亡指数明显低于53BP1激活的肿瘤标本（中位指数，0%比22%；P< 0.05）。001)。在14例原位癌残留患者中，53BP1失活患者的累积局部复发概率明显高于53BP1激活患者(5年时为60% vs. 0%； P=0。020)。综上所述，肝外胆管癌切除后，临床上明显的导管残端局部复发与53BP1失活和细胞凋亡减少密切相关。

This study aimed to clarify the early DNA damage response mediated by 53BP1 in tumor specimens of ductal resection margins and to elucidate its predictive value for clinically evident local recurrence at ductal stumps in 110 patients undergoing resection for extrahepatic cholangiocarcinoma. Ductal margin status was the only independent risk factor for local recurrence(P=0. 001). The cumulative probability of local recurrence at 5 years was 10%, 40%, and 100% in patients with negative ductal margins, positive with carcinoma in situ, and positive with invasive carcinoma, respectively(P<0. 001). Of the 14 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). Apoptotic index was markedly decreased in tumor specimens with 53BP1 inactivation compared to those with 53BP1 activation(median index, 0% vs. 22%; P<0. 001). Among 14 patients with residual carcinoma in situ, the cumulative probability of local recurrence was significantly higher in patients with 53BP1 inactivation than in patients with 53BP1 activation(60% vs. 0% at 5 years ; P=0. 020). In conclusion, after resection for extrahepatic cholangiocarcinoma, clinically evident local recurrence at ductal stumps is closely associated with 53BP1 inactivation and decreased apoptosis.