Intratumoral interferon regulatory factor (IRF)‐1 but not IRF‐2 is of relevance in predicting patient outcome in ovarian cancer

Abstract

IRF‐1 and IRF‐2 expression was determined by real‐time PCR in 138 ovarian cancer samples and 30 healthy ovarian biopsies and was correlated with the expression of other relevant immunologic parameters and common clinicopathologic variables. Regulation of IRF‐1 and IRF‐2 was evaluated by cytokine treatment of various ovarian cancer cell lines, human peritoneal mesothelial cells and ovarian surface epithelium. IRF‐1 but not IRF‐2 was constitutively over‐expressed in 5 of 7 ovarian cancer cell lines. Both IRFs were inducible with IFN‐γ and to a lesser extent with IL‐1 or TNF‐α, but not with IL‐6. Epidermal growth factor (EGF) treatment down‐regulated both IRFs. In ovarian cancer samples only IRF‐1, but not IRF‐2 mRNA, was up‐regulated when compared with healthy ovarian tissue. IRF‐1 but not IRF‐2 expression was significantly associated with interferon (IFN)‐γ and forkhead box P3 (FoxP3). In univariate survival analysis, strong expression of IRF‐1 and IRF‐2 predicted improved disease‐free survival (DFS) and overall survival (OS). In Cox regression analyses, IRF‐1 retained independent prognostic significance for DFS and OS and IFN‐γ for OS. In contrast to other solid tumors, IRF‐2 expression cannot be regarded as a classic oncoprotein associated with poor prognosis in ovarian cancer. Of the immunologic parameters investigated, intratumoral IRF‐1 expression is the most powerful independent predictor of a favorable clinical outcome.