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 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)-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, intratumoral IRF-1 expression is the most powerful independent predictor of a favorable clinical outcome.
Zeimet
Alain G
AG
Department of Gynecology and Obstetrics, Innsbruck Medical University, Innsbruck, Austria. alain.zeimet@i-med.ac.at
Reimer
Daniel
D
Wolf
Dominik
D
Fiegl
Heidi
H
Concin
Nicole
N
Wiedemair
Annemarie
A
Wolf
Anna M
AM
Rumpold
Holger
H
Müller-Holzner
Elisabeth
E
Marth
Christian
C
D000368:Aged; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D015536:Down-Regulation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism*; D050836:Interferon Regulatory Factor-2 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D016019:Survival Analysis
D017931:DNA Primers; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D012333:RNA, Messenger; D004815:Epidermal Growth Factor