Frequency of the TMPRSS2:ERG gene fusion is increased in moderate to poorly differentiated prostate cancers

Background: Recent reports indicate that prostate cancers ( CaP) frequently over- express the potential oncogenes, ERG or ETV1. Many cases have chromosomal rearrangements leading to the fusion of the 59 end of the androgen- regulated serine protease TMPRSS2 ( 21q22.2) to the 3' end of either ERG ( 21q22.3) or ETV1 ( 7p21.3). The consequence of these rearrangements is aberrant androgen receptor- driven expression of the potential oncogenes, ETV1 or ERG. Aim: To determine the frequency of rearrangements involving TMPRSS2, ERG, or ETV1 genes in CaP of varying Gleason grades through fluorescence in situ hybridisation ( FISH) on CaP tissue microarrays ( TMAs). Methods: Two independent assays, a TMPRSS2 break- apart assay and a three- colour gene fusion FISH assay were applied to TMAs. FISH positive cases were confirmed by reverse transcriptase ( RT) PCR and DNA sequence analysis. Results: A total of 106/ 196 ( 54.1%) cases were analysed by FISH. None of the five benign prostatic hyperplasia cases analysed exhibited these gene rearrangements. TMPRSS2: ERG fusion was found more frequently in moderate to poorly differentiated tumours ( 35/ 86, 40.7%) than in well differentiated tumours ( 1/ 15, 6.7%, p = 0.017). TMPRSS2: ETV1 gene fusions were not detected in any of the cases tested. TMPRSS2: ERG fusion product was verified by RT- PCR followed by DNA sequencing in 7/ 7 randomly selected positive cases analysed. Conclusion: This study indicates that TMPRSS2: ERG gene rearrangements in CaP may be used as a diagnostic tool to identify prognostically relevant sub- classifications of these cancers.