Abstract 2711: JC virus T-Antigen (SV40) is an independent prognostic marker for poor disease free survival in epithelial ovarian carcinoma

Abstract

Abstract Epithelial ovarian cancer is the leading cause of death from gynecologic cancers and because of the pelvic location of the ovaries, the patients present at an advanced stage that is generally incurable. SV40 is a type of polyoma virus has been shown to induce tumors in rodents, transform cells in tissue culture and promote tumor transformation in transgenic mice. Many studies have reported the presence of simian virus 40 (SV40) deoxyribonucleic acid (DNA) or protein in human brain tumors, bone cancers, non-Hodgkin's lymphomas, malignant mesothelioma and other solid epithelial tumors including epithelial ovarian carcinomas. We studied the expression of SV40 in a tissue microarray cohort of 156 epithelial ovarian cancers by immunohistochemistry. The incidence of SV40 expression was 44.3% (58/131) and poorly differentiated carcinomas showed a trend towards higher expression of SV40 as compared to moderately and well differentiated tumors (p=0.0898). Validation of SV40 IHC expression was done by polymerase chain reaction (PCR) assay in selected clinical samples and ovarian cancer cell lines. A good concordance was observed between immunohistochemical expression of SV40 and amplification by PCR. Earlier studies have reported various molecular targets of SV40: up-regulation of c-MET oncogene and IGF-1; inhibition of tumor suppressor genes like p53, RASS1FA and protein phosphotase PP2A. To elucidate the link between these targets and SV40 we assessed the immunohistochemical expression of p53, RASS1FA, PP2A, c-MET and IGF-1 the cohort of epithelial ovarian carcinomas. In addition we also analyzed the association of SV40 with known oncogenic mutations in p53, KRAS and PIK3CA genes. SV40 expression showed a significant association with presence of p53 mutation (p<0.0001.) as well as p53 overexpression (p<0.0001). In addition, SV40 expression was associated with overexpression of c-MET (p=0.0111) and IGF-1(p=0.0334). EOC patients with SV40 expression had a poor progression free survival (PFS) of 13.2 months as compared to 20 months with absent SV40 expression (p=0.0980). In the multivariate analysis using Cox Proportional Hazard model for multiple factors like age, FIGO stage, grade, the relative risk was 1.70 for high SV40 expression (95% CI 1.10 – 2.69; p=0.0227) and 2.32 for high stage group III-IV (95% CI 1.33 – 3.90; p=0.0038). Thus, SV40 over expression was an independent prognostic marker in EOC. Altogether, our data highlights the prognostic utility of SV40 as a prognostic biomarker and confirms the well-known effect of SV40 on down-regulation or inactivation of p53, and activation of c-MET/IGF-1 in the epithelial ovarian carcinogenesis. 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 2711. doi:10.1158/1538-7445.AM2011-2711