Relative Copy Number Gain of MYC in Diagnostic Needle Biopsies is an Independent Prognostic Factor for Prostate Cancer Patients

Abstract

ObjectivesWe have recently shown using comparative genomic hybridization (CGH) that 8q gain is an independent predictor of poor survival for prostate cancer patients. Because CGH may be difficult to implement in the clinical practice, we tested the feasibility of using a three-color fluorescent assay to assess 8q status in diagnostic, paraffin-embedded biopsy samples from prostate cancer patients. MethodsFluorescence in situ hybridization with a dual-color probe flanking the MYC gene at 8q24 and a control probe for chromosome 18 was performed in a retrospective series of paraffin-embedded biopsies from 60 prostate cancer patients. The prognostic significance of 8q status was assessed by calculating disease-specific survival curves for these patients. ResultsWhereas 44 (73%) samples displayed copy number gains of the MYC gene, a MYC/CEP18 ratio ≥ 1.5 was detected in 36 (60%) samples. Kaplan-Meier curves with log-rank test showed that patients whose tumors displayed MYC/CEP18 ratio ≥ 1.5 had a significantly worse disease-specific survival (p=0.003). The dual-color labelling of the MYC probe further allowed us to detect structural rearrangements of this gene in six (10%) carcinomas. ConclusionsWe show that a standard fluorescent protocol can successfully be applied to diagnostic needle biopsies to identify relative 8q gain in prostate carcinomas and that patients with a MYC/CEP18 ratio ≥ 1.5 present a significantly higher risk of dying from the disease. The prognostic significance of this genetic variable was seen even for patients with Gleason score 7 or clinical stage II/III carcinomas, whose clinical behavior is currently difficult to predict.