Castration-resistant prostate cancer is the second most common cause of cancer death and results in a median survival of less than 2 years. In prostate cancer, fusions between TMPRSS2 and ERG are common. The ERG rearrangement prevalence in local recurrent castration-resistant prostate cancer compared to distant metastatic prostate cancer is unknown. We investigated the frequency of ERG rearrangement in local recurrent castration-resistant prostate cancer compared to distant metastatic prostate cancer, and assessed for associations between androgen receptor (AR) amplification and ERG rearrangement status. Samples from 134 patients diagnosed with prostate cancer (84 local recurrent castration resistant prostate cancer, 55 distant metastatic prostate cancer) were assessed for their ERG rearrangement and AR amplification status by fluorescence in situ hybridization. Statistical analysis was performed using the χ 2 test. We found that the ERG rearrangement occurs at a significantly lower frequency in distant metastatic prostate cancer (25 %) than in local recurrent castration-resistant prostate cancer (45 %). The AR amplification frequencies were 45 and 35 % in local recurrent castration-resistant prostate cancer and distant metastatic prostate cancer, respectively. The ERG rearrangement occurred at a lower frequency in distant metastatic prostate cancer compared to local recurrent castration-resistant prostate cancer.

AIMS:ERG rearrangements, mostly resulting in TMPRSS2-ERG fusions, are frequent alterations in prostate cancer (PCa), with a frequency ranging from 15% to 78%. As the reason for this variability is unknown, our aim was to investigate the ERG rearrangement frequency with a cohort design.METHODS AND RESULTS:We assessed three well-defined cohorts for ERG rearrangements, using fluorescence in situ hybridization (FISH). The first cohort comprised 119 prostatectomy specimens. The second and third cohorts included incidentally diagnosed PCa [71 cystoprostatectomy specimens, and 105 transurethral resection of the prostate (TURP) specimens]. Seventy of 119 (59%) cases of the prostatectomy cohort harboured ERG rearrangements. Regarding zonal origin, 2/11 (18%) transition zone (TZ) foci and 75/145 (52%) peripheral zone (PZ) foci harboured ERG rearrangements. Within the cystoprostatectomies, 24/71 (34%) cases harboured ERG rearrangements. Regarding zonal origin, 2/9 (22%) TZ foci and 26/86 (30%) PZ foci harboured ERG rearrangements. PCa incidentally identified by TURP harboured ERG rearrangements in 31/105 (29%) cases.CONCLUSIONS:ERG rearrangements occur in TZ PCa, although at a lower frequency than in PZ PCa. We confirmed that approximately half of all prostatectomies harbour ERG rearrangements. However, the frequency in incidentally diagnosed PCa cohorts was significantly lower, even if multifocality was considered. Consequently, zonal origin and cohort design are key for studying the clinical implications of ERG rearrangements.