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

哺乳动物抑癌基因Int6和缺氧诱导因子(HIF)-2α在卵巢癌中的表达

基本信息

批准号：
20591941
负责人：
OHIRA Satoshi
金额：
$ 3万
依托单位：
Shinshu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591941/
关键词：
卵巣癌 Int6 HIF VHL INT6

项目摘要

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.

为了探讨Int 6在卵巢癌中的作用，我们采用免疫组化方法检测了Int 6、HIF-2α和VHL在卵巢癌中的表达，并分析了Int 6、HIF-2α和VHL在卵巢癌患者中的表达与预后的关系。我们检测了70例卵巢癌组织中Int 6、HIF-2α和VHL的表达。分析Int 6、HIF-2α和VHL的表达与胃癌的相关性及预后差异。我们发现Int 6和VHL蛋白表达于肿瘤细胞的胞浆中。卵巢癌细胞中HIF-2α主要表达于胞浆，但偶见胞核染色。HIF-2α在FIGO III+IV期肿瘤中胞浆表达明显高于I+II期肿瘤。在晚期胃癌中，HIF-2α表达与Int 6表达呈负相关。HIF-2α与VHL表达无明显相关性。Log-rank检验显示肿瘤细胞胞浆中HIF-2α免疫染色阳性与卵巢癌患者的不良预后相关（p=0.005）。有趣的是，在HIF-2α阳性和Int 6免疫染色阴性的患者中，预后明显较差。提示HIF-2α亚基表达增高和Int 6表达降低可能参与卵巢癌的发生发展。