The clinicopathologic significance of hypoxia inducible factor 1 alpha expression in ovarian serous tumors

Aim: The hypoxia-inducible factor (HIF) is an alpha (alpha) / beta (beta) heterodimeric DNA binding complex and directs an extensive transcriptional response involving the induction of genes relevant to tumor progression, such as angiogenesis, glucoseenergy metabolism, cellular growth, metastasis, and apoptosis. HIF-1 alpha has also emerged as an attractive target for cancer therapy. The aim of this study is to investigate the association between tissue HIF-1 alpha expression, prognostic significance, and the clinicopathologic features of ovarian serous tumors. Materials and Methods: HIF-1 alpha expression was studied by immunohistochemistry (IHC) in a total of 82 formalin-fixed, paraffin-embedded specimen of ovarian serous tumors. Results: In this series, there were 34 ovarian high grade serous carcinoma, 12 borderline, and 36 benign serous tumors. Statistically it was determined that the expression of HIF-1 alpha was positive, usually in carcinomas or borderline serous tumors, while it was negative in benign serous tumors (p = 0.043). The overall survival of patients with tumors that stained strongly for HIF-1 alpha (mean 22 months) was not significantly different than that of patients with tumors that stained weakly or were negative (mean 27 months) for HIF-1 alpha (p = 0.812). Conclusion: The results suggest that the role of hypoxia may change according to the aggressive and invasive natures of ovarian tumors. In addition the present findings demonstrated the presence of a correlation between HIF-1 alpha expression and serous carcinomas. Therefore expression of HIF-1 alpha may also confer chemoresistance in high-grade serous carcinomas.