Abstract B74: Elafin drives poor outcome in high-grade serous ovarian cancers and basal-like breast tumors

Abstract

Abstract High grade serous ovarian carcinoma (HGSOC) and basal-like breast cancer (BLBC) share many features including TP53 mutations, genomic instability and poor prognosis. We recently reported that Elafin is overexpressed by HGSOC and is associated with poor overall survival. Here, we confirmed that Elafin overexpression is associated with shorter survival in 1000 HGSOC patients. Elafin confers a proliferative advantage to tumor cells through activation of the MAP kinase pathway. This mitogenic effect can be neutralized by RNA interference, specific antibodies, and a MEK inhibitor. Elafin expression in patient-derived samples was also associated with chemoresistance and strongly correlates with bcl-xL expression. We translated these findings into examination of 1100 primary breast tumors and 6 breast cancer cell lines. We observed that Elafin is overexpressed and secreted specifically by BLBC tumors and cell lines, leading to a similar mitogenic effect through activation of the MAP kinase pathway. Here too, Elafin overexpression is associated with shorter overall survival, suggesting that it may serve as a biomarker or therapeutic target in this setting. Citation Format: Intidhar Labidi-Galy, Adam Clauss, Vivian Ng, Sekhar Duraisamy, Kevin M. Elias, Erhan Bilal, Rachel A. Davidowitz, Yiling Lu, Gayane Badalian-Very, Hui-Ying Piao, Un-Beom Kang, Scott Ficarro, Shridar Ganesan, Gordon B. Mills, Jarrod Marto, Ronny Drapkin. Elafin drives poor outcome in high-grade serous ovarian cancers and basal-like breast tumors. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B74.