OBJECTIVE: Epithelial ovarian cancer is associated with high mortality, mostly because of delayed diagnosis, necessitating the search for novel diagnostic and prognostic markers. Here we evaluated the association between expression levels of phosphatase and tensin homolog (PTEN), hypoxia-inducible factor (HIF)-1 alpha, and vascular endothelial growth factor (VEGF), and ovarian cancer. PATIENTS AND METHODS: Expressions of these proteins were assessed by immunohistochemistry in 21 specimens of normal ovary tissues and 76 specimens of ovarian cancer tissues. Associations with pathological characteristics and prognosis were determined using chi-square test, Kaplan-Meier method, log-rank test, and Cox regression model. RESULTS: Expression of PTEN in ovarian cancer tissue was negatively associated with clinical stage and differentiation degree. A reverse trend was observed in association between expression of HIF-1 alpha and VEGF, and the clinical stage of the disease. PTEN expression negatively correlated with HIF-1 alpha and VEGF expression levels, whereas both latter positively correlated with each other. The overall survival of patients with positive PTEN expression was significantly longer than that of those with negative expression; the opposite trend was observed with HIF-1 alpha and VEGF. The differentiation degree and expressions of HIF-1 alpha and PTEN were dependent predictors, whereas VEGF expression, clinical stage and lymph node metastasization were independent prognostic factors in these patients. CONCLUSIONS: PTEN, HIF-1 alpha, and VEGF were found to be prognostic markers in ovarian cancer, with VEGF also being as an independent prognostic factor. Combined detection of their expression levels may be useful for determination of the degree of malignancy, metastasis, and prognosis of ovarian cancer.