Hypoxia-inducible factor 1 alpha ( HIF-1α) gene expression in human ovarian carcinoma

Abstract

Hypoxia-inducible factor 1α (HIF-1α) that regulates genes involved in response to hypoxia and promotes neo-angiogenesis, is a transcriptional factor for vascular endothelial cell growth factor (VEGF). The aim of this study was to examine the expression of HIF-1α and VEGF gene expressions and their relation to angiogenesis, clinicopathologic variables and survival in the patient with human ovarian carcinoma. We retrospectively analyzed HIF-1α and VEGF gene expression levels using reverse transcriptase polymerase chain reaction (RT-PCR) in 60 ovarian carcinomas. Intratumoral microvessel density (IMD) was assessed by immunostaining endothelial cells, using anti-CD 31 antibody in frozen sections. The relationships between the expression level of these genes, IMD and clinicopathologic variables were evaluated by Student's t-test and chi-square tests. Survival analysis was performed by Kaplan–Meier curves. HIF-1α or VEGF gene expression level was independent of age, clinical stage and histological subtype besides grade of tumor. There was no relationship between HIF-1α or VEGF gene expression level and IMD in all carcinomas ( R=0.118 and 0.224, respectively). In addition, a weak association between HIF-1α and VEGF gene expression level was observed ( R=0.300, P=0.020). The association between VEGF gene expression and IMD was observed ( R=0.501, P=0.016). However, no association between IMD and HIF-1α gene expression was observed. Further, both HIF-1α and VEGF gene expression levels had no effect on survival in the patient with ovarian carcinoma. These results suggest that VEGF upregulated by HIF-1α gene may be involved in angiogenesis of some type of ovarian carcinoma, but the expression levels of both genes have no effect on survival in the patients with ovarian carcinoma.