肝内胆管结石合并胆管癌组织中erbB家族蛋白表达及其临床意义

The protein expression of erbB family in tissues of hepatolithiasis combined with bile duct carcinoma and its clinical significance

目的 :探讨肝内胆管结石合并胆管癌组织中erb B1(EGFR)和erb B2(HER2)的表达差异及其临床意义。方法 :收集94例肝内胆管结石合并肝内胆管癌患者的肝内胆管癌组织和50例癌旁肝组织样本,组织切片后进行EGFR和HER2免疫组化染色检测,分析癌与癌旁组织的表达差异;对部分患者进行EGFR分子靶向治疗(埃罗替尼,Erlotinib,150 mg/d,1个疗程),并进行5年无瘤生存分析。结果:两组EGFR阳性表达率分别为58.5%(55/94)和26.0%(13/50),差异有统计学意义(P<0.001);两组HER2阳性表达率分别为33.0%(31/94)和16.0%(8/50),差异有统计学意义(P<0.05)。在胆管癌组中,EGFR和HER2阳性患者的肿瘤组织学分级、浸润深度和肝门淋巴结转移明显高于阴性患者,差异有统计学意义(P<0.05)。在胆管癌患者中EGFR或HER2阳性患者的5年无瘤生存率显著低于阴性患者(P<0.05)。进一步分子靶向治疗发现,EGFR阳性患者埃罗替尼治疗后生存期延长,5年无瘤生存率较EGFR和HER2均阳性者高(81.3%vs.59.4%),但差异无统计学意义(P>0.05)。结论:EGFR和HER2高表达在肝内胆管结石合并肝内胆管癌的发生发展中可能发挥重要作用,且二者高表达与肿瘤的恶性程度以及临床预后密切相关,并可能对临床分子靶向治疗具有指导意义。

Objective：To in vestigate the expression differences of erb B1（EGFR） and erb B2（HER2） in tissues of hepatolithiasis combined with bile duct carcinoma and its clinical significance. Methods： We collected 94 intrahepatic bile duct carcinoma tissues of patients with hepatolithiasis combined with intrahepatic bile duct carcinoma and 50 liver tissues adjacent to carcinoma samples.EGFR and HER2 were detected by immunohistochemical staining after biopsy. Then, we analyzed the expression differences between carcinoma tissues and tissues adjacent to carcinoma. EGFR molecule targeted therapy was performed in some patients（Erlotinib, 150 mg / d,one course of treatment）, and 5-year-disease-free survival rate was analyzed. Results： EGFR positive expression rate of the two groups was 58.5%（55 / 94） and 26.0%（13 / 50）, respectively, and the difference was statistically significant（P〈0.001）; HER2 positive expression rate of the two groups was 33.0%（31 / 94） and 16.0%（8 / 50）, respectivley, and the difference was statistically significant（P〈0.05）. In the bile duct carcinoma group, tumor histologic grading, infiltrating depth and hilus lymph node metastasis of EGFR and HER2 positive patients were obviously higher than those of the negative patients, and the difference was statistically significant（P〈0.05）. In patients with cholangiocarcinoma, 5-year disease-free survival rate of EGFR or HER2 positive patients was significantly lower than that of the negative patients（P〈0.05）. Further found in the molecular targeted therapy, EGFR positive patients treated with erlotinib could extend survival, and 5-year disease-free survival rate was higher than that of EGFR and HER2 positive patients（81.3% vs. 59.4%）, but there was no statistically significant difference（P〉0.05）. Conclusion： EGFR and HER2 expression in patients with intrahepatic bile duct stone combined with the occurrence of intrahepatic cholangiocarcinoma may play an important role in the development, and the two high expression are closely related to the degree of malignant tumor and clinical prognosis, and may has a guiding significance in clinical molecular targeted therapy.