TMPRSS2-ERG Gene Fusion Is Not Associated with Outcome in Patients Treated by Prostatectomy

Abstract

A significant number of prostate cancers have been shown to have recurrent chromosomal rearrangements resulting in the fusion of the androgen regulated TMPRSS2 promoter to a member of the ETS transcription factor family, most commonly ERG. This results in ERG overexpression which may have a direct causal role in prostate tumorigenesis or progression. However, the clinical significance of the rearrangement is unclear and, in particular, relationship to outcome has been inconsistent in recent reports. We analyzed TMPRSS2-ERG gene rearrangement status by fluorescence in situ hybridization (FISH) in 521 cases of clinically localized surgically treated prostate cancer with 95 months median follow-up and also in 40 unmatched metastases. 42% of primary tumors and 40% of metastases had rearrangements. 11% had copy number increase (CNI) of the TMPRRS2-ERG region. Rearrangement alone was associated with lower grade, but not with stage, biochemical recurrence, metastases or death. CNI with and without rearrangement was associated with high grade and advanced stage. Further, a subgroup of cancers with CNI and rearrangement by deletion, with two or more copies of the deleted locus, tended to be more clinically aggressive. DNA index assessment revealed that the majority of tumors with CNI of TMPRSS2-ERG had generalized aneuploidy/ tetraploidy in contrast to tumors without TMPRSS2-ERG CNI, which were predominantly diploid. We therefore conclude that translocation of TMPRSS2-ERG is not associated with outcome and the aggressive clinical features associated with CNI of chromosome 21 reflect generalized aneuploidy and are not due to CNI specifically of rearranged TMPRSS2-ERG.

Genomic Predictors of Outcome in Prostate Cancer

“…Ten studies reported the prognostic value of the gene fusion in radical prostatectomy (RP) cohorts [19][20][21][22][23][24][25][26][27][28]. In 6 of the 10 studies, TMPRSS2:ERG fusion status was not associated with outcome after surgery [19,21,22,24,27,29].…”

Detection ofERGgene rearrangements andPTENdeletions in unsuspected prostate cancer of the transition zone

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14] More recently, several studies demonstrated significant association between ERG rearrangements and PTEN genomic deletions in localized PCA with prognostic implications. [15][16][17][18][19][20] Moreover, studies in transgenic mouse models confirmed that both aberrant expression of ERG and deletion of PTEN are required to develop frank invasive carcinoma, indicating that both genetic aberrations play an important role in driving prostate cancer development and progression. More comprehensive studies are, however required to determine the prognostic significance of these biomarkers for the future clinical management of PCA.…”

Prostate cancer of transition zone origin lacks TMPRSS2–ERG gene fusion

“…Nam et al 6 found that TMPRSS2-ERG expression was the single most significant predictor of disease relapse after surgery, independent of prostate-specific antigen (PSA) level, tumor grade, and tumor stage. However, Gopalan et al 7 recently reported that TMPRSS2-ERG gene fusion was not associated with tumor pathological stage, biochemical recurrence, metastasis, or with the overall survival of the patient in a study of more than 500 patients. Therefore, the clinical significance of TMPRSS2-ERG gene fusion in prostate cancer remains uncertain.…”