ERG protein expression in prostate and vascular tumors: A potential for ERG-based stratification.

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e15171 Background: Frequent overexpression of ERG in prostate tumors is a result of prevalent gene fusions involving upstream sequences of androgen regulated genes (predominantly TMPRSS2) and downstream coding sequences of nuclear transcription factors within the ETS gene family (primarily ERG). Despite numerous reports of ERG alterations at the transcript and genome levels, the ERG oncoprotein remains to be defined. Using a highly specific ERG monoclonal antibody, we have recently developed a comprehensive insight into ERG expression in various cell types of benign and malignant prostate glands. Further, we have analyzed ERG protein expression in human tumors of diverse origins. Methods: Using whole-mount prostate sections from 150 prostatectomy specimens, ERG protein expression was analyzed in PIN, tumor foci, benign glands and other cell types in prostate. In randomly selected cases ERG protein expression was correlated with ERG fusion status. A broad range of vascular endothelial (n=250), other mesenchymal (n=973), and epithelial tumors (n=657) were examined. Results: CPDR ERG-MAb showed striking specificity for detecting prostate tumor cells (>99.9%). Specimens from 65% patients had one or more ERG positive tumor focus. Examination of ERG positive PINs and ERG positive tumors within the same whole-mount sections revealed a 97% concordance. In normal adult tissues, including human and mouse prostate, ERG was restricted to endothelial cells and a subset of bone marrow precursors. ERG was expressed in virtually all vascular tumors and absent in all epithelial tumors except prostate tumors. Conclusions: Taken together, the homogeneous and strong ERG expression in individual tumors and the remarkable correlation between ERG positive PIN lesions and tumors suggests a role for ERG in the pre-invasive to invasive transition of prostate cancer cells. The demonstrated high specificity of CPDR ERG-MAb has potential to provide new opportunities in prostate cancer diagnosis and stratification. Further, ERG is a highly specific new marker for benign and malignant vascular tumors.