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Clinical Significance of IEX-1 Expression in Ovarian Carcinoma

Background: The stress-inducible immediate early response gene X-1 (IEX-1) regulates cell proliferation and apoptosis in a cell type and stimulus-dependent manner. The aim of this study was to investigate IEX-1 expression and its role in apoptosis of ovarian epithelial tumors for potential use in clinical diagnosis and therapy. Methods: IEX-1 expression was examined in paraffin-embedded specimens from 77 patients with epithelial ovarian tumors using immunohistochemistry. Correlation between IEX-1 expression and other clinicopathological parameters was evaluated. Apoptosis of tumor cells was detected by terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL). Results: IEX-1 expression was significantly lower in ovarian cancers compared to cystadenomas and borderline tumors (p < .05). The expression was significantly associated with FIGO stage and histological grade (p < .05), but not with age, histological type, or residual tumor (p > .05). A positive correlation was also observed between IEX-1 expression and apoptotic index (p < .01) or survival (p = .005). Conclusion: With the development of epithelial ovarian tumors from benign to malignant, IEX-1 expression is decreased, concomitant with a decreased rate of cell apoptosis. Thus, IEX-1 is pro-apoptotic in the development of epithelial ovarian cancer. The pro-apoptotic activity may take part in restraining tumor growth at the early stage of ovarian epithelial cancer, whereas its decreased expression probably contributes to the abnormal survival advantage for malignant cancer. Altered IEX-1 expression can potentially be a new predictor of the malignant transformation and a prognostic indicator for cancer therapy.