目的探讨WWOX(WW domain-containing oxidoreductase)基因在非小细胞肺癌(NSCLC)组织中的表达及其临床意义。方法用免疫组化方法检测50例鳞癌,31例腺癌及20例癌旁正常组织中WWOX基因蛋白的表达,并分析其与各临床病理指标、细胞增殖之间的关系。结果WWOX基因在72.8%的NSCLC中失表达或表达减少,而在相邻正常肺组织中有80.0%正常表达。WWOX基因的表达与组织类型、腺癌细胞分化程度密切相关(r=0.262,r=0.457,P〈0.05),在鳞癌和低分化腺癌中WWOX基因失表达或表达减少。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)。Ki67的表达与吸烟、组织分化、临床分期、淋巴结转移密切相关(均P〈0.05);与WWOX蛋白表达呈负相关(r=-0.252,P〈0.05)。结论WWOX蛋白在NSCLC组织中呈低表达,其表达的缺失可能在不同类型NSCLC的形成中发挥了不同的作用,而且与肿瘤的恶性程度及侵袭有关。Ki67蛋白的高表达提示预后不佳。
Objective To study the expression and significance of WWOX gene in non-small cell lung carcinoma (NSCLC). Methods WWOX protein expression was evaluated by immunohistochemistry in 81 NSCLC patients (50 squamous cell carcinomas, 31 adenocarcinomas and 20 adjacent normal lung tissues) and was correlated with histopathologic and clinical characteristics (histotype, grade, tumornode-metastasis, stage, age, gender, index of cell proliferation Ki67 ). Results WWOX expression was absent or reduced in 72. 8% of NSCLC, whereas it was normal in 80. 0% of adjacent normal lung tissues. WWOX expression was strongly associated with tumor histology and histologic grade of adenocarcinoma ( r = 0. 262/0. 457 ,P 〈 0. 05 ), the percentage of cases with absent/strongly reduced WWOX expression was higher in squamous cell carcinomas and in poorly differentiated adenocarcinoma. Finally, WWOX expression intensity was negatively related to the high index of cell proliferation ( r = - 0. 252, P 〈 0. 05 ). Conclusions The loss of WWOX expression plays different roles in tumorigenesis of distinct histotypes of NSCLC and is related to high aggressiveness of tumors.