肝细胞肝癌中Wnt5a、β-catenin和E-cadherin蛋白的表达及临床意义

Expression of Wnt5a,β-catenin and E-cadherin in hepatocellular carcinoma and its clinical significance

目的初步探讨Wnt5 a、β-catenin和E-cadherin的表达与肝细胞肝癌(HCC)发生、发展和转移的关系。方法采用免疫组化ABC及EnVision方法,检测30例HCC(包括10例尸检样本)癌旁、癌组织中Wnt5a、β-catenin和E-cadherin的表达,结合Ki-67进行统计学分析。结果对比于癌旁组织,83%(25/30)的HCC癌组织内Wnt5a蛋白低或缺失表达(P<0.001),其异常表达还相关于高的肿瘤分期(P=0.010)、高的Ki-67指数(P=0.013),以及β-catenin(P=0.025)和E-cadherin(P=0.003)的膜下降表达。癌组织中β-catenin膜下降表达相关于E-cadherin的膜下降表达(P=0.047)。80%(24/30)HCC癌组织中E-cadherin膜下降表达,相关于高的肿瘤分期(P=0.048)、高的K i-67指数(P=0.042)和尸检组肿瘤转移的发生(P=0.033)。结论Wnt5a缺失表达是HCC进展中的频发事件,并相关于β-catenin和E-cadherin的异常表达。Wnt5a在HCC中发挥肿瘤抑制基因样的作用,该蛋白极可能是一个有用的HCC预后不良指标。

Purpose To analyze the expression of Wnt-5a, β-catenin and E-cadherin in hepatocellular carcinomas （HCCs）. Methods Thirty HCCs （including 10 autopsy cases） were examined Wnt-Sa, β-catenin, E-cadherin, and Ki-67 by ABC or EnVision immunohistochemicial method. Results Loss of Wnt-Sa protein expression, evident in 83 % of the HCCs （ n = 25 ）, was significantly associated with higher tumor stage （P = 0. 010）, low membranous expression of β-catenin and E-cadherin （P =0. 025 and P = 0. 003, respectively）, and high Ki-67 L/s （P = 0. 013 ）. Reduced membranous β-catenin expression was significantly associated with low E-cadherin expression （ P = 0. 047 ） in HCC. Low E-cadherin expression was observed in 24 of 30 （ 80% ） tumors that associated with the higher tumor stage （P=0. 048）, high Ki-67 L/s （P=0. 042）, and metastasis in autopsy group （P =0. 033）. Conclusions The cytoplasmic loss of Wnt-Sa protein is a frequent progression event in HCC and associated with abnormal expression of β-catenin and E-cadherin. Our data support the notion that Wnt-Sa retains tumor suppressor function and may be a useful indicator of prognosis in HCC.