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

为了阐明Int6在卵巢癌中的可能参与，我们检测了Int6、HIF-2α和von Hippel-Lindau （VHL）在卵巢癌中的免疫组织化学表达，并根据Int6、HIF-2α和VHL在卵巢癌患者中的表达分析其预后差异。我们检测了70例卵巢癌组织中Int6、HIF-2α和VHL的免疫组化表达。此外，我们还分析了Int6、HIF-2α和VHL的表达与预后的相关性和差异。我们发现肿瘤细胞的细胞质中有Int6和VHL蛋白的表达。HIF-2α染色主要见于细胞质，细胞核染色在卵巢癌细胞中偶见。HIF-2α在FIGO III+IV期肿瘤的细胞质表达明显高于I+II期。在晚期病例中，HIF-2α的表达与Int6的表达呈负相关。HIF-2α与VHL表达无显著相关性。log-rank检验显示，肿瘤细胞中HIF-2α免疫染色细胞质阳性与卵巢癌患者预后不良相关（p=0.005）。有趣的是，在HIF-2α阳性和Int6免疫染色阴性的患者中，预后明显较差。这些结果表明，HIF-2α亚基的表达升高和Int6的表达降低可能参与了卵巢癌的发展。

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.