Antibody-Based Detection of ERG Rearrangement-Positive Prostate Cancer.
Kyung Park, Scott A Tomlins, Kumaran M Mudaliar, Ya-Lin Chiu, Raquel Esgueva, Rohit Mehra, Khalid Suleman, Sooryanarayana Varambally, John C Brenner, Theresa MacDonald, Abhishek Srivastava, Ashutosh K Tewari, Ubaradka Sathyanarayana, Dea Nagy, Gary Pestano, Lakshmi P Kunju, Francesca Demichelis, Arul M Chinnaiyan, Mark A Rubin. Weill Cornell Medical College, New York, NY; University of Michigan, Ann Arbor; Roche Group, Tucson, AZ
Background: TMPRSS2-ERG gene fusions occur in 50% of prostate cancers and result in the over-expression of a chimeric fusion transcript that encodes a truncated ERG product. Previous attempts to detect the product have been hindered by a lack of specific antibodies.
Design: We characterize a rabbit anti-ERG monoclonal antibody (clone EPR 3864, Epitomics) using immunoblotting on prostate cancer cell lines, synthetic TMPRSS2- ERG constructs, chromatin immunoprecipitation and immunofluoresence. We correlated ERG protein expression with the presence of ERG gene rearrangements in prostate cancer tissues using a combined IHC and FISH analysis. We independently evaluated two patient cohorts and observed ERG expression confined to prostate cancer cells and high-grade prostatic intraepithelial neoplasia associated with ERG-positive cancer, as well as vessels and lymphocytes.
Results: Image analysis of 131 cases demonstrated nearly 100% sensitivity for detecting ERG rearrangement prostate cancer, with only 2 of 131 cases demonstrating strong ERG protein expression without any known ERG gene fusion. The combined pathology evaluation of 207 patient tumors for ERG protein expression had 95.7% sensitivity and 96.5% specificity for determining ERG rearrangement prostate cancer.
Conclusions: This study qualifies a specific anti-ERG antibody and demonstrates exquisite association between ERG gene rearrangement and ERG protein expression. Given the ease of performing IHC versus FISH, ERG protein expression may be useful for molecularly subtyping prostate cancer based on ERG rearrangement status and suggests clinical utility in prostate needle biopsy evaluation.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 1:00 PM
Poster Session II # 106, Monday Afternoon