Prevalence of TMPRSS2-ERG Fusion Prostate Cancer among Men Undergoing Prostate Biopsy in the United States

Abstract

Purpose Fusion of the TMPRSS2 prostate-specific gene with the ERG transcription factor is a putatively oncogenic gene rearrangement that is commonly found in prostate cancer tissue from men undergoing prostatectomy. However, the prevalence of the fusion was less common in TURP samples from a Swedish cohort of incidental prostate cancer patients followed by watchful waiting, raising the question as to whether the high prevalence in prostatectomy specimens reflects selection bias. We sought to determine the prevalence of TMPRSS2-ERG gene fusion among PSA-screened men undergoing prostate biopsy in the United States. Experimental design We studied 140 prostate biopsies from the same number of patients for TMPRSS2-ERG fusion status with a FISH assay. 134 (100 cancer and 34 benign) were assessable. Results ERG gene rearrangement was detected in 46% prostate biopsies that were found to have prostate cancer and in 0% of benign prostate biopsies (p<0.0001). Evaluation of morphological features showed that cribriform growth, blue-tinged mucin, macronucleoli and collagenous micronodules were significantly more frequent in TMPRSS2-ERG fusion positive prostate cancer biopsies than gene fusion negative prostate cancer biopsies (p≤0.04). No significant association with Gleason score was detected. In addition, non-Caucasian patients were less likely to have positive fusion status (p=0.02). Conclusions This is the first prospective North American multi-center study to characterize the TMPRSS2-ERG prostate cancer prevalence in a cohort of patients undergoing needle biopsy irrespective of whether or not they subsequently undergo prostatectomy. Our results show that this gene rearrangement is common among North American men who have prostate cancer on biopsy, is absent in benign prostate biopsy, and is associated with specific morphological features. These findings indicate a need for prospective studies to evaluate the relationship of TMPRSS2-ERG rearrangement with clinical course of screening-detected prostate cancer in North American men, and development of non-invasive screening tests to detect TMPRSS2-ERG rearrangement.

Abnormal Expression of the ERG Transcription Factor in Prostate Cancer Cells Activates Osteopontin

“…This frequency of TMPRSS2:ERG fusions is in the range reported from studies conducted in Western countries (38,39). Among these TMPRSS2:ERGþ tumors, 96% were also positive for OPN expression.…”

ETS rearrangements in prostate cancer

“…42 As part of an Early Detection Research Network study sponsored by the National Cancer Institute, we prospectively determined that 46% of men with prostate cancer detected on 12-core needle biopsies by PSA screening harbor TMPRSS2:ERG fusion. 43 This result is consistent with the surgical cohorts. Taken together, observations made over the past several years, from a number of studies since the original description of TMPRRSS2:ETS prostate cancer, suggest that the majority of prostate cancers currently detected by PSA-screening harbor either the common TMPRSS2:ERG (46%) fusion, or one of the less common fusions involving TMPRSS2 or other 59 prime partners (5%-10%).…”

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

“…24 In other studies, TMPRSS2-ERG fusion detected by FISH was present in only 15-30% of prostate cancer diagnosed at transurethral resection for benign prostate hyperplasia. 6,25 While prostate cancer at diagnostic prostate needlebiopsies showed TMPRSS2-ERG fusion in 46% by FISH, 26 our group recently found nuclear ERG overexpression in 61% using immunohistochemistry. 10 The description of a novel ERG antibody in 2010 highly facilitates detection of ERG genomic fusions in clinical specimens.…”