Abstract 30: ERG oncoprotein expression in prostate cancer: Potential for ERG-based stratification

Abstract

Abstract Introduction: Prevalent gene fusions involving regulatory sequences of the androgen receptor (AR) regulated prostate associated genes (predominantly TMPRSS2) and protein coding sequences of nuclear transcription factors in the ETS gene family (primarily ERG), result in frequent overexpression of ERG in prostate tumors. Emerging studies suggest oncogenic functions of ERG in prostate cancer (CaP). Despite numerous reports of gene fusions and mRNA expression, ERG oncoprotein in CaP still remains to be defined. Using an anti-ERG monoclonal antibody (ERG-MAb) developed by our group, a global view of ERG oncoprotein expression has been established in the context of multi-focal CaP. Experimental procedures: Specificity of the ERG MAb was established using wt ERG and TMPRRSS2-ERG encoded proteins expressed in HEK 293 cells and ERG si RNA treated VCaP cells harboring TMPRRSS2-ERG fusion. ERG expression in formalin fixed paraffin embedded (FFPE), whole mount-prostate specimens was optimized by immuno-histochemistry assay. TMPRSS2-ERG fusion status in representative specimens was analyzed by b-DNA assay or fluorescent in situ hybridization (FISH). Results: Through exhaustive evaluations of 132 whole-mount prostates (227 tumor foci and over 200,000 benign glands), we demonstrate 99.9 % specificity of an anti-ERG monoclonal antibody. Specimens from over 60% patients had one or more ERG positive tumor focus. Over 80% concordance was noted between the presence of ERG protein and the common TMPRSS2-ERG fusion (A type) transcript in representative specimens from 35 pateints. Conclusions: Unequivocal association of focally ERG positive PIN lesions with ERG positive carcinoma (80 out of 80 specimens) and vice versa (52 out of 52 specimens) strongly affirms biological role of ERG in clonal progression of prostate tumors. Taken together, the homogeneous and strong ERG expression in individual tumors establishes the potential for ERG based stratification of prostate cancers. Funding sources: NIH Grants RO1 DK065977 and Center for Prostate Disease Research Program HU001-04-C-1502 Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 30.