Prognostic significance of hypoxia-induced autophagy related markers in malignant surface epithelial ovarian tumors

Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3), a pro-apoptotic protein, regulates autophagy. BNIP3 is induced in hypoxic cells, being regulated by hypoxia-inducible factor 1- (HIF1-). The role of hypoxia-induced autophagy in surface epithelial ovarian carcinomas (EOC) is not well established. This work aimed to evaluate BNIP3 and HIF1- immunohistochemical expression and study the relation between their expression and patients’ survival in EOC patients.

High BNIP3 and HIF1- expressions were associated with a high tumor grade (p = 0.012 and 0.013), stage III tumors (p = 0.031 and 0.035), presence of omental deposits (p = 0.029 and 0.004), presence of capsular invasion (p = 0.010 and 0.019), and presence of vascular invasion (p = 0.033 and 0.007). High BNIP3 and HIF1- expressions were associated with shortened overall survival (OS) (p = 0.021 and 0.029) and poor disease-free survival (DFS) (p = 0.002 and 0.005). The relation between BNIP3 and HIF1- immunohistochemical expression was statistically significant (p < 0.001).

High BNIP3 and HIF1- expressions are related to unfavorable clinicopathological parameters in terms of higher tumor grade, advanced tumors, presence of omental deposits, capsular and vascular invasion, together with poor OS and DFS in malignant surface epithelial ovarian tumor patients.