Predictive Biomarkers and Personalized Medicine ERG Rearrangement for Predicting Subsequent Cancer Diagnosis in High-Grade Prostatic Intraepithelial Neoplasia and Lymph Node Metastasis

Purpose: We aimed to analyze whether ERG rearrangement in biopsies could be used to assess subsequent cancer diagnosis in high-grade prostatic intraepithelial neoplasia (HGPIN) and the risk of lymph node metastasis in early prostate cancer. Experimental Design: Samples from 523 patients (361with early prostate cancer and 162withHGPIN) were collected prospectively. On the basis of the cutoff value established previously, the 162 patients with HGPIN were stratified to two groups: one with an ERG rearrangements rate 1.6% (n 1⁄4 59) and the other with an ERG rearrangements rate <1.6% (n 1⁄4 103). For the 361 prostate cancer cases undergoing radical prostatectomy, 143hadpelvic lymphnodedissection (node-positive, n1⁄456 andnode-negative, n1⁄487). All ERG rearrangement FISH data were validated with ERG immunohistochemistry. Results:A total of 56 (of 59, 94.9%)HGPIN cases with an ERG rearrangements rate 1.6%and5 (of 103, 4.9%) HGPIN cases with an ERG rearrangements rate <1.6% were diagnosed with prostate cancer during repeat biopsy follow-ups (P < 0.001). Therewere significant differences in ERG rearrangement rates between lymph node–positive and -negative prostate cancer (P < 0.001). The optimal cutoff value to predict lymph node metastasis by ERG rearrangement was established, being 2.6% with a sensitivity at 80.4% [95% confidence interval (CI), 67.6–89.8] and a specificity at 85.1% (95%CI, 75.8–91.8). ERGprotein expression by immunohistochemistry was highly concordant with ERG rearrangement by FISH. Conclusions: The presence of ERG rearrangement in HGPIN lesions detected on initial biopsy warrants repeat biopsies and measuring ERG rearrangement could be used for assessing the risk of lymph node metastasis in early prostate cancer. Clin Cancer Res; 1–10. 2012 AACR.