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Expression of hypoxia-inducible factor 1α gene affects the outcome in patients with ovarian cancer


Junzo Kigawa, MD, PhD, Department of Obstetrics and Gynecology, Tottori University, School of Medicine, 36-1 Nishimachi, Yonago 683-8504, Japan. Email:


We conducted study to determine whether and how the expression of the hypoxia-inducible factor 1α (HIF-1α) gene relates to outcome in patients with epithelial ovarian cancer. A total of 66 patients with epithelial ovarian cancer, who underwent primary surgery followed by platinum-based chemotherapy, were entered into this study. We confirmed the expression of HIF-1α and the vascular endothelial growth factor (VEGF) by immunohistochemistry. To determine the quantity of HIF-1α and VEGF expression, messenger RNA of each gene was measured by real-time reverse transcription–polymerase chain reaction. The cutoff values were determined by the receiver-operating characteristic curve according to survival. The protein expressions of HIF-1α and VEGF were strongly observed in the cancer cells. The cutoff value of HIF-1α and VEGF gene expression was 6.0 and 3.0, respectively. The expression of HIF-1α did not relate to clinical stage, but tumor with low VEGF expression was observed more frequently in stage I patients. The response rate to chemotherapy did not differ between high and low expression of both genes. The overall survival for patients with high expression of HIF-1α was significantly lower, but disease-free survival did not differ between high and low expression of HIF-1α, whereas both overall and disease-free survival for patients with high expression of VEGF were significantly lower. Multivariate analysis revealed that FIGO stage and HIF-1α expression were independent prognostic factors but that VEGF was not. The present study suggested that the expression level of HIF-1α could be an independent prognostic factor in epithelial ovarian cancer.