ERG Gene Translocation Predicts Progression of High Grade Prostatic Intraepithelial Neoplasia to Prostate Cancer
Kyung Park, James T Dalton, Ramesh Narayanan, Michael L Hancock, David G Bostwick, Mitchell S Steiner, Mark A Rubin. Weill Medical College of Cornell University, New York, NY; GTx, Inc., Memphis, TN; Bostwick Laboratories, Inc., Glen Allen, VA
Background: High grade prostatic intraepithelial neoplasia (HGPIN) is the precursor lesion of prostate cancer (PCA) and as many as 40% of patients with HGPIN will be diagnosed with PCA within three years and up to 80% within eight years. ERG gene fusion, an early event in PCA development, is found in 15% of HGPIN. In this study, we interrogated retrospectively the role of ERG gene fusion in the progression of HGPIN to PCA in the context of a clinical trial.
Design: The GTx Protocol G300104 randomized 1,590 men with HGPIN to receive toremifene 20 mg orally per day or placebo for three years or until a diagnosis of prostate cancer was made on prostate needle biopsy. As part of this phase III clinical trial, a central pathologist (DB) evaluated prostate needle biopsies of subjects with isolated HGPIN at baseline, 12, 24, and 36 months follow-up biopsies. ERG immunohistochemistry was performed on biopsies from 462 subjects and evaluated for protein over-expression. Statistical analysis was completed to correlate the IHC and clinical data.
Results: ERG expression was detected in 11.1 % (51/461) of subjects with isolated HGPIN. 37.5% of 461 subjects developed PCA during the three year clinical trial. With 53% (27/51) of ERG-positive (not in the same core as the PCA+ core) and 35% (143/410) of ERG-negative subjects progressing to PCA, subjects that expressed ERG were more likely to develop prostate cancer (P=0.012, chi-square test). ERG expression was not associated with Gleason score. Prostate cancer free survival (Kaplan-Meier 3 year estimate, 1SE) was significantly (p=0.008, log-rank test) worse among patients expressing ERG (32.5%, 9%) than those who did not express ERG (56.0%, 3.6%).
Conclusions: The results of this Phase III clinical trial represent the largest prospective study of men with isolated HGPIN. The cancer detection rate on repeat biopsy in year one is higher than that reported in several smaller, retrospective studies. The current standard of care for patients with HGPIN is to monitor PSA levels and progression of HGPIN to cancer through serial prostate biopsies. This study underscores the necessity of more stringent follow-up for men with HGPIN. In addition, ERG fusion status on initial biopsy with isolated HGPIN could be of prognostic importance for PCA development and the clinicians should manage these patients accordingly.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 150, Monday Morning