人表皮生长因子受体2基因在胆囊癌中的表达及其与临床特征和预后的关系

The role played by human epidermal growth factor receptor 2 amplification/overexpression in gallbladder cancer and its association with clinico-pathology and prognosis

目的研究人表皮生长因子受体2(HER2)在胆囊癌中的表达情况,分析其与胆囊癌患者根治性切除术后的临床病理特征及生存期的关系。方法搜集2011年1月至2016年12月中国医学科学院北京协和医学院肿瘤医院收治的50例胆囊癌患者的临床资料,其中男性14例,女性26例,年龄(60.3±8.7)岁。采用免疫组织化学和荧光原位杂交技术检测HER2基因在胆囊癌组织中的扩增和表达情况。依据HER2基因表达情况分为2组:HER2阴性组(n=40)和HER2阳性组(n=10)。通过方差分析研究HER2扩增/过表达与临床病理因素的关系。电话随访患者的预后。Kaplan-Meier法进行生存分析,Cox比例风险模型探讨影响胆囊癌患者根治性切除术预后的因素。结果10例患者胆囊癌组织中存在HER2扩增/过表达,HER2阳性率为20.0%(10/50)。HER2阴性组和HER2阳性组中合并脉管癌栓患者的比例间差异有统计学意义[7.5%(3/40)比30.0%(3/10),P<0.05]。共获得46例患者的随访资料,其中HER2阴性组36例,HER2阳性组10例。与HER2阴性组相比,HER2阳性组患者的中位无复发生存期(10.10比75.07个月)和中位总生存期(16.77比83.07个月)均减少,差异具有统计学意义(均P<0.05)。单因素分析显示,HER2阳性是影响胆囊癌患者根治术后复发和生存的危险因素。多因素Cox回归分析显示,淋巴结转移是影响胆囊癌患者根治性切除术后复发(HR=4.31,95%CI:1.92~9.68,P<0.001)和生存(HR=3.44,95%CI:1.08~11.00,P=0.037)的独立危险因素。结论HER2扩增/过表达与胆囊癌患者的脉管癌栓和不良预后有关。

Objective To study the amplification/overexpression of human epidermal growth factor receptor 2(HER2)in patients with gallbladder cancer,and to analyze the correlation between amplification/overexpression of HER2 with clinicopathological features and survival in patients after R0 resection.Methods There were 14 males and 26 females,aged(60.3±8.7)years old and treated at the Cancer Hospital of Chinese Academy of Medical Sciences from January 2011 to December 2016 who met the inclusion criteria of the study.Immunohistochemistry and fluorescence in situ hybridization were used to detect amplification/expression of HER2 in resected tumor tissues.Patients were divided into two groups according to the HER2 gene expression:the HER2-negative group(n=40)and the HER2-positive group(n=10).The Chi-square test was used to analyze the relationship between amplification/expression of HER2 and clinicopathological parameters.Patients were followed up by telephone for prognosis.The Kaplan-Meier method was used for survival analysis.The Cox proportional hazard model was used to explore factors affecting prognosis of gallbladder cancer patients.Results HER2 amplification/overexpression was found in 10 patients with gallbladder cancer,with a positive rate of HER2 being 20.0%(10/50).There was a significant difference in the proportion of patients with vascular tumor thrombus between the HER2 negative group and the HER2 positive group[7.5%(3/40)vs.30.0%(3/10),P<0.05].On follow-up,data of 46 patients was available.There were 36 patients in the HER2-negative group and 10 patients in the HER2-positive group.Compared with the HER2-negative group,the median recurrence-free survival(10.10 vs.75.07 months)and the median overall survival(16.77 vs.83.07 months)of the HER2-positive group were both significantly lower(both P<0.05)than the HER2-negative group.Univariate analysis showed HER2 positivity to be a risk factor for recurrence-free and overall survival in patients with gallbladder cancer after radical resection.Cox multivariable analysis revealed that lymph node metastasis was an independent risk factor for both recurrence-free(HR=4.31,95%CI:1.92-9.68,P<0.001)and overall survival(HR=3.44,95%CI:1.08-11.00,P=0.037).Conclusion Amplification/overexpression of HER2 was associated with venous invasion and worse prognosis in patients with gallbladder cancer.