卵巢上皮性癌组织中雌激素受体亚型的表达

Expressions of Estrogen Receptor Subtypes in Epithelial Ovarian Carcinomas

目的探讨雌激素受体(estrogen receptor,ER)亚型ERα及ERβ蛋白在卵巢上皮性癌中的表达及其与临床病理学因素及生存的关系。方法应用免疫组化法对118例卵巢上皮性癌组织进行ERα及ERβ检测,对其中10例ERα及ERβ阳性表达的冰冻组织标本,应用激光捕获显微切割技术(laser capture m icod issection,LCM)捕获卵巢癌细胞,应用W estern印迹分析方法检测其蛋白表达水平。结果118例卵巢上皮性癌组织中ERα表达为0级32例(27.1%),1级表达20例(16.9%),2级表达17例(14.4%),3级表达49例(41.5%);ERβ表达为0级表达1例(0.8%),1级表达7例(5.9%),2级表达13例(11%),3级表达97例(82.2%)。ERα蛋白表达在卵巢癌患者不同的年龄、组织学类型、F IGO分期、组织分化程度以及残余肿瘤大小间差异无统计学意义(P>0.05);ERβ蛋白表达在卵巢癌患者的年龄、F IGO分期、残余肿瘤大小间差异无统计学意义(P>0.05),在不同组织分化程度间差异有统计学意义,低分化者显著高于中、高分化者(P<0.05);总生存率在ERα表达各组间比较差异无统计学意义(P>0.05),在ERβ表达各组间比较差异有统计学意义,强表达组生存期明显缩短(P<0.05)。W estern印迹结果与免疫组化结果一致。结论卵巢上皮性癌组织以ERβ表达为主,ERβ蛋白表达与组织分化程度有关。

Objective To investigate the expressions of estrogen receptor（ER） subtypes ERα and ERβ in epithelial ovarian carcinomas. Methods One hundred and eighteen Norwegian patients with epithelial ovarian carcinoma were included in this study. The expressions of ERα and ERβ were examined by means of immunohistochemistry. The relationships between protein expressions and clinicopathological features and survival were analyzed. Frozen tissues from 10 cases in which the tumors showed variable ERα and ERβ protein expressions were used for Laser capture microdissection （LCM）. Cancer cells in each frozen section were captured with the LCM method and processed for Western blot analysis. Results Of the 118 tumours, 32（27.1%）, 20（16.9%）, 17（14.4%）, 49（41.5%） demonstrated negative, weak, moderate and strong expression of ERα protein, respectively; 1（0.8%）, 7（5.9%）, 13（11%）, 97（82.2%） showed negative, weak, moderate and strong expressions of ERβ protein, respectively. There was no significant association between ERα expression and the clinicopathological features such as age, histological type, FIGO stage, histological grade and residual tumour size. ERβ expression was not associated with age, histological type, FIGO stage and residual tumour size, but it was significantly associated with higher histological grade. In addition, Kaplan-meier analysis revealed that high levels of ERβ expression was significantly associated with a shorter overall survival （P=0.03）. Conclusion There are ERα and ERβ expressions in epithelial ovarian carcinomas. Higher level of ERβ protein expression is associated with higher histological grade and poorer clinical outcome in the cases of ovarian carcinoma. ERβ may be a useful marker of ovarian carcinogenesis and could predict the efficacy of endocrinotherapy and the prognosis for patients with ovarian carcinoma.