959 IMMUNOHISTOCHEMICAL EXPRESSION OF ERG ONCOPROTEIN IS ASSOCIATED WITH DEVELOPMENT OF LOCAL RECURRENCE AND PROSTATE CANCER-SPECIFIC DEATH IN MEN TREATED WITH RADICAL PROSTATECTOMY

Abstract

INTRODUCTION AND OBJECTIVES: ETS-Related Gene (ERG) encoded protein is present in a significant portion of prostate adenocarcinoma (PCa) and strongly correlates with TMPRSS2-ERG rearrangement. While ERG oncogenic activation is believed to be a causal genomic alteration in a significant portion of PCa, its prognostic value in disease progression remains uncertain. The aim of this study was to evaluate ERG oncoprotein expression levels in men undergoing radical prostatectomy (RP) to determine whether this was predictive of earlier time to relapse or prostate cancer-specific death. METHODS: Between 1954 and 1997, 1004 consecutive patients underwent RP at Virginia Mason Medical Center in Seattle, WA. Local pelvic disease or disease consistent with regional lymph node metastases was defined by tissue diagnosis or by overt radiographic signs of disease. Washington State death certificates were obtained and PCa had to be the first listed cause of death for the patient to be classified as developing PCa-specific death. Paraffin-embedded tissue samples were available for the majority of men. Thirty-four patients were identified with known adverse outcomes of either distant metastasis or PCa-specific death. These patients were matched by age, PSA and time since surgery with 66 patients who had undergone RP and had not developed advanced disease. The tissue was stained with a highly specific anti-ERG monoclonal antibody, clone 9FY (Furustao et al., PCPD, 2010). Each TMA spot was evaluated by a GU pathologist for ERG staining. A proc-mixed analysis with stage as a random effect was performed to assess statistical significance. RESULTS: The mean follow-up was 10.26 years. ERG oncoprotein expression was detected in 11/31 (35.48%) adverse outcome patients and 15/66 (22.39%) favorable outcome patients, however, this was not significant (p 0.59). The mean expression H-score (cancer nuclear staining intensity multiplied by percent of cancer staining) was significantly higher from the group of patients that developed local recurrence 61.46 vs. 16.36 (p 0.0066) and PCa-specific death 31.36 vs. 13.10 (p 0.0181). CONCLUSIONS: ERG oncoprotein expression alone did not have any discriminative ability. However, degree of ERG expression at time of surgery was highly associated with increased risk of developing local recurrence and PCa-specific death. ERG scoring may be a useful metric to identify patients who would benefit from adjuvant treatment or closer follow-up, allowing more accurate individual patient treatment plans.