Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer

Abstract

The prostate-specific gene, TMPRSS2 is fused with the gene for the transcription factor ERG in a large proportion of human prostate cancers. The prognostic significance of the presence of the TMPRSS2:ERG gene fusion product remains controversial. We examined prostate cancer specimens from 165 patients who underwent surgery for clinically localised prostate cancer between 1998 and 2006. We tested for the presence of TMPRSS2:ERG gene fusion product, using RT -PCR and direct sequencing. We conducted a survival analysis to determine the prognostic significance of the presence of the TMPRSS2:ERG fusion gene on the risk of prostate cancer recurrence, adjusting for the established prognostic factors. We discovered that the fusion gene was expressed within the prostate cancer cells in 81 of 165 (49.1%) patients. Of the 165 patients, 43 (26.1%) developed prostate-specific antigen (PSA) relapse after a mean follow-up of 28 months. The subgroup of patients with the fusion protein had a significantly higher risk of recurrence (58.4% at 5 years) than did patients who lacked the fusion protein (8.1%, Po0.0001). In a multivariable analysis, the presence of gene fusion was the single most important prognostic factor; the adjusted hazard ratio for disease recurrence for patients with the fusion protein was 8.6 (95% CI ¼ 3.6 -20.6, Po0.0001) compared to patients without the fusion protein. Among prostate cancer patients treated with surgery, the expression of TMPRSS2:ERG fusion gene is a strong prognostic factor and is independent of grade, stage and PSA level.

Prostate cancer genes associated with TMPRSS2–ERG gene fusion and prognostic of biochemical recurrence in multiple cohorts

“…Although TMPRSS2 -ERG fusion has typically been reported as prevalent in 40 -50% of prostate tumours, the range has varied by as much as 25 -60% (Nam et al, 2007;Setlur et al, 2008;Sun et al, 2008;Yoshimoto et al, 2008;Hofer et al, 2009;Mosquera et al, 2009). The techniques used for TMPRSS2 -ERG detection, novel potential fusion products and genetic differences in population cohorts may account for these discrepancies.…”

“…Several studies have indicated that TMPRSS2 -ERG fusions confer a worse prognosis (Nam et al, 2007;Attard et al, 2008a;Clark et al, 2008), whereas others have not . Discrepancies in the reported prognostic significance of TMPRSS2 -ERG fusions can be explained in a similar manner by factors affecting the variation in prevalence of TMPRSS2 -ERG (i.e., cohort race/ethnicity, fusion detection technique), and are also liable to the primary end point of the study (i.e., biochemical recurrence, overall survival).…”

“…In an effort to better characterise the molecular implications of TMPRSS2 -ERG fusions in prostate cancer and to identify other genetic prognostic markers, we have utilised RNA extracted from radical prostatectomy specimens in a prospective cohort previously characterised for TMPRSS2 -ERG T1/E4 fusion transcript expression by qualitative PCR (Nam et al, 2007). This cohort (hereafter referred to as the Toronto cohort) of 165 patients had 81 (49%) fusion-positive tumours in which patients with a detectable fusion transcript had a significantly higher risk of biochemical recurrence (58% at 5 years) than did patients whose tumours did not express detectable fusion transcripts (8% at 5 years).…”

ERG immunohistochemistry is not predictive for PSA recurrence, local recurrence or overall survival after radical prostatectomy for prostate cancer

“…8,[19][20][21][22][23] This variability might be due to differences in study cohorts, clinical end points and methodologies for detecting gene fusion. For example, RT-PCR-detected TMPRSS2-ERG fusion was found in more than 70% of patients surgically treated by radical prostatectomy for prostate cancer.…”

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

“…Mehra et al 5 reported that TMPRSS2-ERG gene fusion was statistically associated significantly with high pathological stage. 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.…”