Gene Expression Signature Characterized By Pi3kinase Activation And Stathmin Overexpression Validates To Identify Aggressive Disease And A Potential For Pi3kinase-Inhibitors In Endometrial Carcinomas

Abstract Background: We have recently reported a gene expression signature defining an aggressive subgroup of endometrial cancer patients characterized by PI3Kinase activation and Stathmin overexpression, suggesting the potential for PI3Kinase inhibitors against this disease (Salvesen et al, PNAS 2009). In the present study we wanted to validate the value of these measures for PI3Kinase activation prospectively in an independent patient series. Methods: A prospectively collected, independent patient series of 158 cases of endometrial carcinoma was assessed. Real-time quantitative PCR was performed for the 29 genes in the previously defined gene signature. Stathmin expression in formalin fixed tumor specimens was assessed by immunohistochemistry (IHC). Results: A high signature score predicted shorter recurrence free (p=0.001) and disease-specific survival (p=0.002). A high score was also significantly associated with high age (p=0.04), high FIGO stage (p=0.03), non-endometrioid histology (p<0.001), high grade (p<0.001) and lymph node metastases (p=0.02). High signature score was also correlated with overexpression of Stathmin in tumor tissue (p≪0.002). Conclusion: The finding validates that previously identified markers for PI3Kinase activation identify aggressive phenotype in endometrial cancer. This further supports a potential for PI3Kinase-inhibitors in the treatment of metastatic endometrial carcinoma. We suggest that clinical trials with drugs targeting the PI3Kinase pathway involve stratification related to biomarkers, including the expression levels for this gene signature and Stathmin. 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 330. doi:10.1158/1538-7445.AM2011-330