Expression of TMPRSS2: ERG gene fusion in prostate cancer cells is an important prognostic factor for cancer progression Free

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The prostate-specific gene, TMPRSS2, is fused with the transcription factor gene, ERG in a high proportion of prostate cancers. However, the clinical significance of TMPRSS2:ERG gene fusion among prostate cancer patients is unknown. We assayed for the presence of the TMPRSS2:ERG fusion gene product among 83 patients who underwent surgery for clinically localized prostate cancer using RT-PCR and direct DNA sequencing, and evaluated its prognostic significance. The fusion gene was present within prostate cancer tumor cells in 39 patients (46.4%). Twenty-five patients (29.8%) experienced biochemical disease relapse (elevated PSA) after a mean follow-up of 23.3 months (range 1 to 96 months). Patients with the fusion product had a significantly higher rate of recurrence (5-year recurrence rate 68.4%) compared to patients who lacked the fusion product (5-year recurrence rate 17.1%, p=0.0002). After adjusting for grade, stage and PSA level at diagnosis, the hazard ratio for disease relapse for patients with the fusion gene was 4.8 (95% C.I.: 1.6 - 14, p = 0.004) compared to patients without the fusion. From the multivariate analysis, the presence of gene fusion was the single most important prognostic factor. Our study indicates that the expression of TMPRSS2:ERG fusion gene among prostate cancer patients treated with surgery is a strong prognostic factor for disease relapse, and may have important clinical implications.