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

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-gamma and to a lesser extent with IL-1 or TNF-alpha, but not with IL-6. Epidermal growth factor (EGF) treatment down-regulated both IRFs. In ovarian cancer samples only IRF-1, but not IRIF-2 mRNA, was up-regulated when compared with healthy ovarian tissue. IRF-1 but not IRF-2 expression was significantly associated with interferon (IFN)-gamma 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-gamma 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, intraturnoral IRF-1 expression is the most powerful independent predictor of a favorable clinical outcome. (C) 2008 Wiley-Liss, Inc.