目的探讨WWOX基因蛋白、ErbB2蛋白以及Ki67在非小细胞肺癌组织中的表达及其与细胞增殖之间的关系。方法用免疫组化方法检测81例非小细胞肺癌患者(50例鳞癌,31例腺癌)的肺癌组织以及其中20例患者癌旁正常组织中WWOX基因蛋白、ErbB2蛋白的表达,并分析其与各临床病理指标及其与细胞增殖之间的关系。结果WWOX基因在72.8%(59/81)的非小细胞肺癌中失表达或表达减少,而在相邻正常肺组织中有80.0%(16/20)正常表达(失表达率20.0%)。WWOX基因的表达与组织类型、细胞分化程度、淋巴结转移密切相关(x^2=5.44,P=0.019;x^2=4.740,P=0.029;x^2=4.51,P=0.034),在鳞癌和低分化癌中WWOX基因失表达率或表达减少率较高。肺癌中ErbB2的过度表达与肺癌的临床分期、淋巴结转移相关(x^2=6.90,P=0.009;x^2=5.68,P=0.017),WWOX蛋白阳性表达与ErbB2负相关(r=-0.239,P〈0.05)。细胞增殖指数越高,WWOX基因表达越少,二者呈负相关(r=-0.252,P〈0.05)。结论WWOX蛋白表达的缺失在肺癌的发生中有一定的作用且与肿瘤的恶性侵袭有关。WWOX蛋白的低表达与ErbB2的过表达可以协同判断非小细胞肺癌的预后较差。
Objective To study the expression of WWOX,ErbB2 and Ki67 protein in non-small cell lung cancer(NSCLC) and the relationships with cell proliferation. Methods WWOX and ErbB2 protein expressions were evaluated by immunohistochemistry in 81 NSCLC patients (50 squamous cell carcinomas ,31 adenocarcinomas and 20 adjacent normal lung tissues ) and the correlations with histopathologie cell proliferation were analyzed. Results WWOX expression was absent/reduced in 72.8% of NSCLC, while it was normal in 80.0% of adjacent normal lung tissues. WWOX expression was strongly associated with tumor histology, histologic grade and lymph node metastasis ( X^2 = 5.44, P = 0.019 ; X^2= 4. 740, P = 0. 029, X^2= 4.51, P = 0.034), reduced WWOX expression was higher in squamous cell carcinomas and in poorly differentiated tumors. The overexpression of ErbB2 was associated with TNM stage and lymph node metastasis ( X^2 = 6.90, P = 0. 009 ; X^2= 5.68, P = 0. 017 ). WWOX expression was negatively related to the overexpression of ErbB2 ( r = - 0. 239, P 〈 0.05 ). WWOX expression intensity was negatively related to the high index of cell proliferation ( r = - 0. 252,P 〈 0.05 ). Conclusion The loss of WWOX expression plays different roles in tumorigenesis of NSCLC and is related to high aggressiveness of tumors. The loss of WWOX expression and the overexpression of ErbB2 can estimate the prognosis of NSCLC.