Purpose: To investigate the impact of expression of hypoxia-inducible factor (HIF)-1α on prognosis and on response to chemotherapy in epithelial ovarian tumors.

Experimental Design: Expression of HIF-1α protein was studied by immunohistochemistry in 102 specimens of epithelial ovarian cancers, in 50 borderline tumors, and in 20 cystadenomas. Results were correlated with p53, p21, 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, expression of HIF-1α was observed. There was a significant correlation of HIF-1α protein expression and MVD (P < 0.001). HIF-1α overexpression alone and MVD showed no impact on survival of cancer patients. Furthermore, the response to platinum-based chemotherapy was independent from HIF-1α expression. Expression of HIF-1α correlated with apoptotic rate in the majority of cases, especially in low malignant potential tumors. In contrast, in cancer patients with strong expression of HIF-1α and p53 protein overexpression, not only a significantly increased MVD (P = 0.032, Mann-Whitney test) but also a significantly shorter overall survival was observed (P < 0.0001, Cox regression). The apoptotic rate was very low in these tumors.

Conclusions: HIF-1α protein overexpression alone has no impact on the prognosis of ovarian cancer. The combination of HIF-1α protein overexpression with nonfunctional p53, however, indicates a dismal prognosis.