Early DNA damage response in residual carcinoma in situ at ductal stumps and local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma
Early DNA damage response in residual carcinoma in situ at ductal stumps and local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma
复制标题
肝外胆管癌切除术后导管残端原位癌早期DNA损伤反应及局部复发
DOI：
10.1007/s00534-012-0539-1
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Hatakeyama K
中科院分区：
文献类型：
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作者：
Wakai T;Shirai Y;Sakata J;Korita PV;Ajioka Y;Hatakeyama K
背景/目的本研究旨在阐明p53结合蛋白1（53BP1）介导的残留胆管残端原位癌DNA损伤反应与肝外胆管癌切除患者局部复发的关系。方法对11例导管切缘阳性的原位癌患者进行回顾性分析。为了评估早期 DNA 损伤反应，通过免疫荧光检查了 53BP1 的核染色模式。结果11例原位癌肿瘤标本中，7例显示53BP1在细胞核内弥漫定位（53BP1失活），4例显示离散的53BP1核灶（53BP1激活）。与 53BP1 激活的四个肿瘤样本相比，七个 53BP1 失活的肿瘤样本的细胞凋亡指数显着降低（中位细胞凋亡指数，1 vs. 22%；p=0.003）。 53BP1失活患者的局部复发累积概率显着高于53BP1激活患者（累积5年局部复发率，60 vs. 0%；p=0.019）。结论临床上明显的导管残端原位残留癌局部复发与53BP1失活和细胞凋亡减少密切相关。
Background/purposeThe aim of this study was to clarify the association between the DNA damage response mediated by p53-binding protein 1 (53BP1) in residual carcinoma in situ at ductal stumps and local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma.MethodsA 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 53BP1 was examined by immunofluorescence. TUNEL analysis was used to calculate the apoptotic index.ResultsOf the 11 tumor specimens of carcinoma in situ, seven showed diffuse localization of 53BP1 in nuclei (53BP1 inactivation) and four showed discrete nuclear foci of 53BP1 (53BP1 activation); the apoptotic index was significantly decreased in the seven tumor specimens with 53BP1 inactivation compared to the four with 53BP1 activation (median apoptotic index, 1 vs. 22 %;p= 0.003). The 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).ConclusionsClinically evident local recurrence of residual carcinoma in situ at ductal stumps is closely associated with 53BP1 inactivation and decreased apoptosis.