The expression of mammalian tumor suppressor, Int6 and hypoxia inducible factor(HIF)-2α in ovarian carcinomas

为了阐明Int6在卵巢癌中的可能作用，我们检测了Int6、HIF-2α和von Hippel-Lindau在卵巢癌中的表达，并根据Int6、HIF-2α和VHL的表达分析卵巢癌患者预后的差异。应用免疫组织化学方法检测70例卵巢癌组织中Int6、HIF-2α和VHL的表达。此外，我们还根据Int6、HIF-2α和VHL的表达分析了三者之间的相关性和预后差异。我们发现Int6和VHL蛋白表达于肿瘤细胞的胞浆中。低氧诱导因子-2α染色主要见于胞浆，卵巢癌细胞中偶见核染色。HIF-2α胞浆表达在FIGO III+IV期显著高于I+II期，晚期HIF-2α表达与Int6表达呈负相关。低氧诱导因子-2α表达与VHL表达无明显相关性。LOG-RANK检验显示，肿瘤细胞胞浆HIF-2α阳性表达与卵巢癌患者预后不良有关(p=0.005)。有趣的是，HIF-2α阳性而INT6免疫染色阴性的患者预后明显较差。提示HIF-2Int6亚基表达增加和α表达降低可能参与了卵巢癌的发生发展。

In order to elucidate the possible involvement of Int6 in ovarian carcinomas, we examined the immunohistochemical expression of Int6, HIF-2α and von Hippel-Lindau (VHL) in ovarian carcinomas, and analyzed the prognostic differences according to Int6, HIF-2α and VHL expression in ovarian carcinoma patients. We examined the immunohistochemical expression of Int6, HIF-2α, and VHL in 70 cases of ovarian carcinomas. In addition, we analyzed the correlation and prognostic differences according to the expression of Int6, HIF-2α and VHL. We found that Int6 and VHL protein were expressed in the cytoplasm of tumor cells. Although the HIF-2α staining was mainly observed in the cytoplasm, nuclear staining was sporadically observed in ovarian carcinoma cells. Cytoplasmic expression of HIF-2α was significantly higher in tumors of FIGO stage III+IV than those of stage I+II. In advanced cases, HIF-2α expression showed inverse correlation with the expression of Int6. There was no significant correlation between HIF-2α and VHL expression. The log-rank test showed that the cytoplasmic positive HIF-2α immunostaining in tumor cells is associated with the poor prognosis of ovarian carcinoma patients (p=0.005). Interestingly, the prognosis was significantly poorer in those with positive HIF-2α and negative Int6 immunostaining. These results show that the increased expression of HIF-2α subunit and decreased expression of Int6 may involved in the progression of ovarian carcinoma.