ERG rearrangement for predicting subsequent cancer diagnosis in high-grade prostatic intraepithelial neoplasia and lymph node metastasis
A partir d'échantillons biopsiques prélevés sur 523 patients atteints d'un cancer de la prostate de stade précoce ou présentant une néoplasie intraépithéliale prostatique de haut grade, cette étude évalue l'association entre un réarrangement du gène ERG et le risque de développer la maladie et des métastases ganglionnaires
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 (PCa). Experimental Design: Samples from 523 patients (361 with early PCa and 162 with HGPIN) were collected prospectively. Based on the cutoff value established previously, the 162 patients with HGPIN were stratified to two groups: one with an ERG rearrangements rate ≥1.6% (n=59) and the other with an ERG rearrangements rate <1.6% (n=103). For the 361 PCa cases undergoing radical prostatectomy, 143 had pelvic lymph node dissection (node-positive, n=56 and node-negative, n=87). All ERG rearrangement fluorescence in situ hybridization (FISH) data were validated with ERG immunohistochemistry. Results: 56 (56/59, 94.9%) HGPIN cases with an ERG rearrangements rate ≥1.6% and 5 (5/103, 4.9%) HGPIN cases with an ERG rearrangements rate <1.6% were diagnosed with PCa during repeat biopsy follow-ups (P<0.001). There were significant differences in ERG rearrangement rates between lymph node positive and negative PCa (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% CI: 67.6%-89.8%) and a specificity at 85.1% (95% CI: 75.8%-91.8%). ERG protein 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 PCa.
Clinical Cancer Research , résumé, 2012