Expression of hypoxia-inducible factor 1 alpha in epithelial ovarian tumors: Its impact on prognosis and on response to chemotherapy

Purpose: To investigate the impact of expression of hypoxia-inducible facto r (HIF)-1 alpha on prognosis and on response to chemotherapy in epithelial ovarian tumors. Experimental Design: Expression of HLF-1 alpha. protein was studied by immu nohistochemistry in 102 specimens of epithelial ovarian cancers, in 50 bord erline tumors, and in 20 cystadenomas. Results were correlated with p53, p2 1, and bcl-2 expression, microvessel density (MVD), apoptotic rate of tumor cells, and survival. Results: In 68.6% of ovarian cancers and 88% of borderline tumors, expressi on of HIF-1 alpha was observed. There was a significant correlation of HIF- 1 alpha protein expression and MVD (P < 0.001). HIF-1 alpha overexpression alone and MVD showed no impact on survival of cancer patients, Furthermore, the response to platinum-based chemotherapy was independent from RIP-la! e xpression. Expression of HIF-1 alpha correlated with apoptotic rate in the majority of cases, especially in low malignant potential tumors. In contras t, in cancer patients with strong expression of HIF-1 alpha and p53 protein overexpression, not only a significantly increased MVD (P = 0.032, Mann-Wh itney test) but also a significantly shorter overall survival was observed (P < 0.0001, Cox regression). The apoptotic rate was very low in these tumo rs. Conclusions: HIF-1 alpha protein overexpression alone has no impact on the prognosis of ovarian cancer. The combination of HIF-1 alpha protein overexp ression with nonfunctional p53, however, indicates a dismal prognosis.