TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort

Abstract

The identification of the TMPRSS2:ERG fusion in prostate cancer suggests that distinct molecular subtypes may define risk for disease progression. In surgical series, TMPRSS2:ERG fusion was identified in 50% of the tumors. Here, we report on a population-based cohort of men with localized prostate cancers followed by expectant (watchful waiting) therapy with 15% (17/111) TMPRSS2:ERG fusion. We identified a statistically significant association between TMPRSS2:ERG fusion and prostate cancer specific death (cumulative incidence ratio ¼ 2.7, Po0.01, 95% confidence interval ¼ 1.3-5.8).Quantitative reverse-transcription-polymerase chain reaction demonstrated high estrogen-regulated gene (ERG) expression to be associated with TMPRSS2:ERG fusion (Po0.005). These data suggest that TMPRSS2:ERG fusion prostate cancers may have a more aggressive phenotype, possibly mediated through increased ERG expression.

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

“…From a case -control study by Lapointe et al (2007), where 54 patients with localised cancer and 9 patients with metastasis were examined for fusion status, no correlations were found with stage, grade or recurrence. On the other hand, large cohort studies of patients managed with watchful waiting did show correlations with a positive fusion status being associated with reduced survival (Attard et al, 2007;Demichelis et al, 2007).…”

“…Several studies have compared clinicopathological parameters (Perner et al, 2006;Wang et al, 2006;Lapointe et al, 2007;Rajput et al, 2007;Tu et al, 2007) and prognostic significance (Wang et al, 2006;Attard et al, 2007;Demichelis et al, 2007;Lapointe et al, 2007;Nam et al, 2007) of this gene fusion with conflicting results. Two of these studies showed no correlation between histologic grade (Gleason score) (Lapointe et al, 2007;Tu et al, 2007), while others found positive associations (Attard et al, 2007;Rajput et al, 2007).…”

“…watchful waiting) showed that men who had TMPRSS2:ERG fusion had lower prostate cancer-specific survival compared to men without fusion expression (Attard et al, 2007;Demichelis et al, 2007). Patients managed and selected for watchful waiting from these cohorts have different baseline distributions in grade, stage and PSA level to patients treated with surgery and may not be comparable.…”

Urine markers in monitoring for prostate cancer

“…63 Patients with gene fusions were reported to have significantly higher rates of recurrence than those lacking TMPRSS2/ERG. 64 Furthermore, Demichelis et al 58 found statistically significant association between TMPRSS2/ERG and CaP-specific death in a Swedish population with up to 22 years of clinical follow-up without curative treatment (watchful waiting cohort).…”

“…54 Apropos CaP, the most common variants involve TMPRSS2 exon 1 or 2 fused to ERG exons 2, 3, 4 or 5 55,56 with a prevalence of the exon 4. [57][58][59] Less common combinations include TMPRSS2 exon 4 or 5 fused to ERG exon 4 or 5 59 and TMPRSS2 exon 2 fused to inverted ERG exons 6-4. 60 TMPRSS2/ERG fusion prostate cancers appear to have a more aggressive phenotype and poor prognosis.…”