核因子κB、表皮生长因子受体及黏蛋白1在肝内胆管结石合并肝内胆管癌组织的表达及其意义

摘要

目的 探讨肝内胆管结石合并肝内胆管癌组织核因子κB(NF-κB)、表皮生长因子受体(EGFR)和黏蛋白1(MUCl)的表达及其临床意义。方法取中山大学附属第二医院1989年8月至2009年6月间肝切除组织石蜡标本90例，其中肝内胆管结石合并肝内胆管癌33例为实验组，肝内胆管结石32例为对照组，肝良性肿瘤旁1～2 cm正常肝内胆管组织25例为空白组。组织切片分别进行NF-κB、EGFR及MUC1免疫组化染色，分析其表达差异的意义。结果 3组NF-κB的表达阳性率分别为51.5％(17/33)、25％ (8/32)和4％(1/25)，P＜0.01;3组EGFR的表达阳性率分别为57.6％(19/33)、31.3％ (10/32)和0(o/25)，P＜0.01; MUC1表达阳性率分别为54.5％ (18/33)、28.1％(9/32)和0(0/25)，P＜0.01。EGFR、MUC1在病理组织学分级、肿瘤局部浸润及淋巴结转移的表达差异有统计学意义。肿瘤患者EGFR、MUC1阳性表达者的累积生存率比阴性表达者低(P＜0.01)。结论NF-κB是肝内胆管癌发生的早期事件；NF-κB、EGFR及MUC1过表达在肝内胆管癌发展过程起协同的重要作用，EGFR及MUC1高表达与肿瘤恶性程度以及预后有关。%Objective To investigate the role of nuclear factor kappa B (NF-κB), epidermal growth factor (EGFR) and Mucin 1 (MUC1) in hepatolithiasis associated with intrahepatic cholangiocarcinoma. Methods Specimens were taken from 90 patients who underwent hepatectomies from August 1989 to June 2009 at the Second Affiliated Hospital of Sun Yat-sen University. The specimens were stained immunohistochemically for NF-κB, EGFR and MUC1. There were 33 patients who had hepatolithiasis associated with intrahepatic cholangiocarcinoma (the experiment group). 32 patients with hepatolithiasis served as the control group, and 25 patients with normal intrahepatic bile ducts taken at 1-2cm distal to benign hepatic neoplasm served as the blank group. The immunohistochemical staining were performed on tissue slices. Results NF-κB positive rate was 51.5％ (17/33), 25％(8/32) and 4％ 1/25) in the experiment group, the control group and the blank group respectively,P＜0. 01 ; EGFR positive rates were 57. 6％ (19/33), 31.3％ (10/32) and 0 (0/25) respectively,P＜0. 01; MUC1 positive rates were 54. 5％ (18/33), 28. 1 ％ (9/32), 0 (0/25) respectively,P＜0. 01. There were significant differences for high level expressions of EGFR and MUC1 among histopathologic grading, tumor invasion and metastasis. The survival rates of patients with EGFR and MUC1 expressed tumor were lower than of patients with non-expressed tumout (P＜0. 01). Conclusions NF-κB is probably involved in the early stage of intrahepatic cholangiocarcinogenesis. Overexpressions of NF-κB, EGFR and MUC1 play coordinately and important roles during intrahepatic cholangiocarcinogenesis. High level expressions of EGFR and MUC1 are related to the malignant degree of cholangiocarcinoma and to worse prognosis.