Increased gene copy number of ERG on chromosome 21 but not TMPRSS2–ERG fusion predicts outcome in prostatic adenocarcinomas

Abstract

The role of TMPRSS2–ERG gene fusion in prostate cancer prognostication remains controversial. We evaluated the prognostic role of TMPRSS2–ERG fusion using fluorescence in situ hybridization analysis in a case–control study nested in The Johns Hopkins retropubic radical prostatectomy cohort. In all, 10 tissue microarrays containing paired tumors and normal tissues obtained from 172 cases (recurrence) and 172 controls (non-recurrence) matched on pathological grade, stage, race/ethnicity, and age at the time of surgery were analyzed. All radical prostatectomies were performed at our institution between 1993 and 2004. Recurrence was defined as biochemical recurrence, development of clinical evidence of metastasis, or death from prostate carcinoma. Each tissue microarray spot was scored for the presence of TMPRSS2–ERG gene fusion and for ERG gene copy number gains. The odds ratio of recurrence and 95% confidence intervals were estimated from conditional logistic regression. Although the percentage of cases with fusion was slightly lower in cases than in controls (50 vs 57%), the difference was not statistically significant (P=0.20). The presence of fusion due to either deletion or split event was not associated with recurrence. Similarly, the presence of duplicated ERG deletion, duplicated ERG split, or ERG gene copy number gain with a single ERG fusion was not associated with recurrence. ERG gene polysomy without fusion was significantly associated with recurrence (odds ratio 2.0, 95% confidence interval 1.17–3.42). In summary, TMPRSS2–ERG fusion was not prognostic for recurrence after retropubic radical prostatectomy for clinically localized prostate cancer, although men with ERG gene copy number gain without fusion were twice more likely to recur.

Adaptation and clonal selection models of castration‐resistant prostate cancer: Current perspective

“…89 Although the TMPRSS2-ERG fusion gene is highly relevant in androgen-dependent prostate cancer, it has been shown to be bypassed in late stage castrationresistant prostate cancer in which oncogenic ERG is overexpressed through other mechanisms independent of TMPRESS2. 91 From the above discussion it is obvious that there is evidence for and against either model. However, genetic/ epigenetic aberrations previously thought to be exclusively or predominantly associated with advanced prostate cancer are now increasingly detected in early and premalignant disease because of the increasing sophistication and sensitivity of current assay techniques.…”

The proto‐oncogeneERGis a target of microRNAmiR‐145in prostate cancer

“…It has been known for more than 15 years as proto-oncogene with mitogenic and transforming activity [19,20]. [22], and an increased gene copy number of wildtype ERG has recently shown to be prognostic for PCa recurrence [23]. We detected over-expression of ERG mRNA and protein in the majority of analyzed PCa cases, while miR-145 exhibited an inverse regulation pattern.…”

TMPRSS2-ERG gene fusion in prostate cancer

“…Since 2005, when Tomlins 6 first described the presence of this fusion in PCa, a large number of studies have been published in this field. Some authors found a correlation between the presence of fusion and poor prognosis 36,44,[69][70][71] , but others found a correlation between the presence of fusion and good prognosis [72][73][74] or no correlation 31,[75][76][77][78] . The prognostic value of TMPRSS2-ERG rearrangements in selected studies is summarized in Table 1.…”

“…Prognostic value of TMPRSS2-ERG rearrangements in selected studies. 78 . They reported that TMPRSS2-ERG gene fusion was not associated with PCa recurrence, supporting the lack of prognostic significance of the ERG gene fusion determined by FISH.…”