Background: The discovery of ERG/ETV-1-gene rearrangements and PTEN-gene loss suggests their use in a mechanism-based prognostic classification of prostate cancer (PCa).

Purpose: To evaluate the potential clinical significance and natural history of different disease categories by combining ERG/ETV-1-gene rearrangements and PTEN-gene loss status.

Methods: We utilized fluorescence in situ hybridization (FISH) assays to detect PTEN-gene loss and ERG/ETV-1-gene rearrangements in 308 conservatively managed PCa patients with survival outcome data.

Results: ERG/ETV-1-gene rearrangements alone and PTEN-gene loss alone each failed to show a link to survival in multivariate analyses. However, there was a strong interaction between ERG/ETV-1-gene rearrangements and PTEN-gene loss (p<0.001). The largest subgroup of patients (54%), lacking both PTEN-gene loss and ERG/ETV-1-gene rearrangements comprised a ‘good prognosis’ population exhibiting favourable cancer-specific survival (85.5% alive at 11 years). The presence of PTEN-gene loss in the absence of ERG/ETV-1-gene rearrangements identified a patient population (6%) with poorer cancer-specific survival that was highly significant (HR = 4.87, p<0.001 in multivariate analysis, 13.7% survival at 11 years) when compared to the ‘good prognosis’ group. ERG/ETV-1-gene rearrangement and PTEN-gene loss status should now prospectively be incorporated into a predictive model to establish whether predictive performance is improved.

Conclusions: Our data suggest that FISH studies of PTEN-gene loss and ERG/ETV-1-gene rearrangements could be pursued for patient stratification, selection and hypothesis-generating sub-group analyses in future PCa clinical trials and potentially in patient management.

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 662.