EphA2受体及其配体在浆液性卵巢癌中的表达及其临床意义

Expression and Prognostic Significance of EphA2 and EphrinA1 in Ovarian Serous Carcinomas

目的探讨浆液性卵巢癌组织中EphA2及其配体EphrinA-1的蛋白表达、定位及其与临床病理学因素及生存的关系。方法应用免疫组织化学方法检测浆液性卵巢癌组织中EphA2及其配体EphrinA-1的蛋白表达、定位,并应用免疫组织化学方法、逆转录-聚合酶链反应(RT-PCR)和Western blot分析方法联合检测卵巢癌细胞系OVCAR3、SKOV3中EphA2及其EphrinA-1 mRNA及蛋白质表达水平。结果 95例浆液性卵巢癌组织中,EphA2和EphrinA-1蛋白阳性表达率分别为92.6(88/95)和97.9(93/95),高于正常卵巢组织〔40%(8/20)和30%(6/20),P=0.000〕;EphA2阳性染色定位于肿瘤区和血管内皮细胞,EphrinA-1阳性染色主要定位于肿瘤区,二者的阳性表达呈正相关(r=0.98,P=0.02);EphA2和EphrinA-1蛋白表达与浆液性卵巢癌患者的年龄、FIGO分期、残余肿瘤大小及组织分化程度均无相关性,二者强表达与患者生存差有关(P<0.05)。卵巢癌细胞系OVCAR3及SKOV3在mRNA及蛋白质水平均存在EphA2和EphrinA-1的高表达。结论 EphA2与EphrinA-1蛋白可能在浆液性卵巢癌的发展过程中起着协同促进作用,EphA2与EphrinA-1蛋白的强表达与浆液性卵巢癌患者的生存差有关,提示二者具有潜在的预后价值。

Objective To investigate the expression and prognostic significance of EphA2 and EphrinA-1 in ovarian serous carcinomas.Methods Ninety five tumors from the patients with ovarian serous carcinomas and 2 ovarian cancer cell lines were recruited.The expressions of EphA2 and EphrinA-1 were examined by means of immunohistochemistry.The relationships among protein expression and clinicopathological features,survival of patients were analyzed.The mRNA and protein expressions of EphA2 and EphrinA-1 in ovarian cancer cell lines were measured with semiquantitative polymerase chain reaction and western blotting.Results The protein expressions of EphA2 and EphrinA-1 in tumor were 92.6%（88/95）and 97.9%（93/95）respectively,while were 40%（8/20） and 30%（6/20） in adjacent ovarian tissue（P=0.000）.EphA2 immunohistochemical staining could be observed in both tumour and vascular endothelial cells,and EphrinA-1 mainly localized in the tumor cells.The expression of EphA2 was significantly associated with the expression of EphrinA-1（r=0.98,P=0.02）.There was no significant correlation between the expressions of EphA2/EphrinA-1 and age,FIGO stage,residual tumour size and histological grade.High levels of both EphA2 and EphrinA-1 protein expression were significantly associated with a shorter overall survival in multivariate analysis（P〈0.05）.High levels of EphA2 and EphrinA-1 mRNA and protein were detected in OVCAR3 and SKOV3 cell lines.ConclusionThere are over-expression of EphA2 and EphrinA-1 in ovarian serous carcinomas and ovarian cancer cell lines.Tumours with higher expression levels of both EphA2 and EphrinA-1 significantly associated with poorer clinical outcome.