Prostate cancer (PCa) tumors harboring translocations of ETS family genes with the androgen responsive TMPRSS2 gene (ETS+ tumors) provide a robust biomarker for detecting PCa in approximately 70% of patients.
However, the prognostic value of AMACR expression and its relation to TMPRSS2-ERG gene rearrangement as one of the most common molecular alterations in PCA is not fully explored.
Majority of prostate cancer (PCa) patients carry TMPRSS2/ERG (T/E) fusion genes and there has been tremendous interest in understanding how the T/E fusion may promote progression of PCa.
Chromosomal translocations that juxtapose the androgen-sensitive transmembrane protease, serine 2 (TMPRSS2) gene promoter to the oncogenic ETS-family transcription factor ERG result in excessive ERG overexpression in approximately 50% of prostate cancer (PCa) patients.
In view of the fact that molecular differences between the zones may explain this difference, combined with the findings that translocations between TMPRSS2 and several ETS members are frequently observed in PCA, we hypothesized that the ETS family may be crucial to explaining this difference.
During last years, new promising biomarkers such as Prostate Cancer Antigen 3 (PCA-3) and TMPRSS2-ETS fusion genes have been evaluated for their clinical use.
The T-allele of the Met160Val variant in TMPRSS2, which has been associated with the TMPRSS2-ERG fusion, may be informative of time to PCA diagnosis for a subset of high-risk Caucasian men who are undergoing regular PCA screening.
If confirmed, this could have significant clinical impact in further stratifying patients with PCA should the TMPRSS2-ERG be confirmed as a prognostic biomarker.
If we consider the high incidence of PCA and the high frequency of this gene fusion, TMPRSS2-ERG is the most common genetic aberration so far described in human malignancies.