Abstract 408: Expression of interferon-stimulated gene 15 is a novel prognostic predictor for patients with advanced stage high-grade serous ovarian adenocarcinoma

Abstract

Abstract Objectives: Utilizing the transcriptome profiling approach to identify genes that are differentially expressed in normal ovaries, and serous borderline ovarian tumors of low-malignant potential (LMP), and low-grade ovarian serous carcinomas compared with high-grade ovarian serous carcinomas (HGSC), we identified ISG15, an ubiquitin-like molecule that is strongly up regulated by type I interferon, to be highly up-regulated in advanced stage HGSCs. We seek to validate the expression patterns of ISG15 and correlated them with clinical outcomes. Methods: Over-expression of ISG15 was confirmed in ovarian cancer cell lines and tissue by real time PCR and immunohistochemistry, respectively. Immunolocalizaation of ISG15 was performed on 155 HGSCs, 10 serous LMPs, 10 normal ovaries, and 10 fallopian tubes. Expression levels of ISG15 were quantified by Image-Pro plus software. The correlation between overall survival and progression free survival and ISG15 expression levels was performed on 155 and 130 HGSC, respectively, using both Kaplan Meier and Cox Regression analyses. Results: ISG15 expression was not detected in normal ovaries, fallopian tubes and LMPs. Over-expressed of ISG15 was confirmed in a majority of HGSC cell lines and tumor tissue. To further evaluate the clinical significance of nuclear ISG15 expression, both Cox and Kaplan-Meier analyses were performed on patients with HGSC. Multivariate Cox analysis showed that ISG15 expression levels were associated with improved overall survival (HR:0.9, P=0.011). In addition, using median ISF15 staining intensity as a cut-off, Kaplan-Meier analysis and log rank test demonstrated that strong ISG15 expression was associated with improved overall and progression free survival (P<0.001 and P=0.002, respectively). Conclusion: Over-expression of ISG15 is common in high-grade serous ovarian adenocarcinoma. The expression levels in tumor cells are strongly correlated with overall survivals, suggesting ISG15 may be a powerful prognostic marker for patients with HGSC. Further functional studies on the functional role of ISG15 in ovarian cancer progression are warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 408. doi:10.1158/1538-7445.AM2011-408