Abstract 5122: Characterizing the molecular features of ERG positive tumors in primary and castration resistant prostate cancer.

Abstract

Abstract Metastatic castration-resistant prostate cancer (CRPC) has a poor prognosis and remains a significant therapeutic challenge. Gene fusions between the TMPRSS2 gene and members of the ETS family of transcription factors (ERG, ETV-1 ETV-4 and 5) have been found in prostate cancer (PCa). In this study we hypothesized that the overexpression of ERG in PCa promotes the expression of common genes and pathways in nuclear ERG positive hormone sensitive primary PCa and metastatic CRPC tumors. Our objective was to identify these common genes and pathways. Using LuCaP PCa xenografts developed at the University of Washington, specimens obtained at radical prostatectomy, and metastatic specimens obtained at rapid autopsy, 3 sets of tissue microarrays were made from 24 LuCaP PCa xenograft lines, 114 radical prostatectomies and 155 metastases from 50 autopsy patients who died from CRPC (with up to 4 metastases from each patient). Nuclear ERG expression was analyzed by immunohistochemistry (IHC). In addition, to characterize the molecular features of ERG expressing PCa, 24 LuCaP PCa xenografts, 24 radical prostatectomies, and 78 corresponding metastases were also assessed by Agilent gene expression analysis. Consistent with previously published FISH and qRT-PCR analyses, IHC revealed that 7 of 24 LuCaP xenograft lines were nuclear ERG positive. Fifty-one of 114 primary prostate cancers were nuclear ERG positive. However, among the 155 CRPC metastases from 50 autopsy patients, 15 of 155 metastases had nuclear ERG positivity. These 15 metastases represent 7 of 50 patients with at least 1 nuclear ERG positive metastasis. This suggests that nuclear ERG expression is less frequent in CRPC than in hormone sensitive primary prostate carcinomas. Furthermore, not all metastases in a given patient were nuclear ERG positive. In addition, gene expression data was generated from 24 LuCaP PCa xenografts, 24 radical prostatectomies and 78 CRPC metastases, which were grouped into ERG positive and ERG negative metastases based on nuclear ERG positivity in the same tissue specimen by IHC. The gene expression profiles of the ERG positive and ERG negative cancer tissues are being analyzed to identify ERG regulated genes and ERG regulated pathways of interest. This study is a comprehensive analysis of ERG expression and downstream effectors of ERG in xenograft models of PCa, primary PCa and CRPC. Our data suggest that ERG expression is less frequent in CRPC and nuclear ERG status can vary from site to site within a CRPC patient. The gene expression studies will further define the role of ERG in PCa. Citation Format: Martine Roudier, Ilsa Coleman, Xiaotun Zhang, Roger Coleman, Lisly Chéry, Lisha Brown, Bryce Lakely, Celestia Higano, Lawrence D. True, Paul H. Lange, Shiv Srivistava, Aykut Üren, Eva Corey, Robert L. Vessella, Peter S. Nelson, Colm Morrissey. Characterizing the molecular features of ERG positive tumors in primary and castration resistant prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5122. doi:10.1158/1538-7445.AM2013-5122