ERG protein expression reflects hormonal treatment response and is associated with Gleason score and prostate cancer specific mortality.

Background: ERG (ETS regulated gene) protein expression has been shown to reflect ERG genomic rearrangements in prostate cancer (PCA). However, ERG protein expression prognostic value has not been yet investigated.

Design: ERG protein expression was investigated in a cohort of 312 men with PCA diagnosed in transurethral resection of the prostate.

Results: ERG expression was detected in 76/293 (25.9%) of patients. Overall ERG expression was associated with Gleason score (GS) (p<0.0001), tumour volume (p=0.04) and with cancer specific mortality (p=0.15). Low ERG intensity was significantly associated with higher GS (p=0.02) and marginally with cancer specific mortality (p=0.11). The association with cancer specific mortality was more significant in patients without any hormonal manipulation (p=0.02). Multivariate Cox model using GS, tumour volume and ERG intensity to predict time to cancer specific death yielded a marginally significant effect for high versus low ERG protein expression (hazard ratio (HR)=0.36; 95% confidence interval (CI): 0.10-1.38; p=0.14) and a non-significant effect for GS >7 (HR=4.85; 95%CI: 0.48, 48.65; p=0.18). Men with ERG expression showed longer free progression time to castration resistant disease compared to men with no ERG expression (mean 11.39 versus 6.1 months, p=0.08).

Conclusion: We report significant association between ERG protein levels and each of GS, progression to castration resistant and cancer specific mortality. High ERG intensity was associated with lower GS, better overall survival and longer free progression times to castration resistant disease. ERG protein levels may have prognostic and therapeutic role in PCA and should be investigated in future studies.