The TMPRSS2:ERG Rearrangement, ERG Expression, and Prostate Cancer Outcomes: A Cohort Study and Meta-analysis.
ABSTRACT Whether the genomic rearrangement transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (ERG) has prognostic value in prostate cancer is unclear.
Among men with prostate cancer in the prospective Physicians' Health and Health Professionals Follow-Up Studies, we identified rearrangement status by immunohistochemical assessment of ERG protein expression. We used Cox models to examine associations of ERG overexpression with biochemical recurrence and lethal disease (distant metastases or cancer-specific mortality). In a meta-analysis including 47 additional studies, we used random-effects models to estimate associations between rearrangement status and outcomes.
The cohort consisted of 1,180 men treated with radical prostatectomy between 1983 and 2005. During a median follow-up of 12.6 years, 266 men experienced recurrence and 85 men developed lethal disease. We found no significant association between ERG overexpression and biochemical recurrence [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.78-1.26] or lethal disease (HR, 0.93; 95% CI, 0.61-1.43). The meta-analysis of prostatectomy series included 5,074 men followed for biochemical recurrence (1,623 events), and 2,049 men followed for lethal disease (131 events). TMPRSS2:ERG was associated with stage at diagnosis [risk ratio (RR)(≥T3 vs. T2), 1.23; 95% CI, 1.16-1.30) but not with biochemical recurrence (RR, 1.00; 95% CI, 0.86-1.17) or lethal disease (RR, 0.99; 95% CI, 0.47-2.09).
These results suggest that TMPRSS2:ERG, or ERG overexpression, is associated with tumor stage but does not strongly predict recurrence or mortality among men treated with radical prostatectomy. Impact: This is the largest prospective cohort study to examine associations of ERG overexpression and lethal prostate cancer among men treated with radical prostatectomy. Cancer Epidemiol Biomarkers Prev; 21(9); 1497-509. ©2012 AACR.
- SourceAvailable from: David M Marcus[Show abstract] [Hide abstract]
ABSTRACT: To determine the impact of multiparametric magnetic resonance imaging (MP-MRI) of the prostate on established risk stratification criteria in patients with clinically localized adenocarcinoma of the prostate (ACP). The cohort included 71 patients who underwent MP-MRI of the prostate at a tertiary care referral center as part of their initial workup for ACP. Tumor characteristics comprising traditional risk stratification criteria (prostate-specific antigen, clinical T stage, and biopsy Gleason score) were recorded, and the initial National Comprehensive Cancer Network risk group was calculated. The National Comprehensive Cancer Network risk group was then recalculated incorporating MRI findings. The impact of MRI findings on changes in risk group classification was evaluated using the Stuart-Maxwell test. For patients undergoing radical prostatectomy, MRI findings were correlated with pathologic findings. The cohort included 11 (15.5%), 39 (54.9%), and 21 patients (29.6%) with low-, intermediate-, and high-risk disease, respectively. MRI findings led to risk group upstaging in 12 cases (16.9%). The highest yield was demonstrated in patients with intermediate-risk disease, in whom MRI led to upstaging in 25.6% of patients. There was a significant difference between pre-MRI and post-MRI risk group classifications (P <.01) for the entire cohort. Compared with radical prostatectomy specimens, the specificity of MRI for T3 disease was 92.9%. In our cohort of patients undergoing MP-MRI for previously untreated, clinically localized ACP, MRI findings led to changes in risk stratification in a substantial proportion of patients. Our findings support the use of MP-MRI in the workup of patients with localized ACP.Urology 04/2014; · 2.42 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: For patients newly diagnosed with prostate cancer, the most significant question is whether the 'truly malignant' disease has been identified. This review will provide an overview of current prostate cancer genomic and biomarker discovery - validation strategies geared towards identifying aggressive, clinically significant disease at the time of diagnosis. Based on recent findings the prostate cancer aggressive disease phenotype develops as a result of mutations (TP53, PTEN), structural events (TMPRSS2-ETS), epigenetic changes (EZH2, DAB2IP, histone alteration), and transcriptional modifications (SChLAP, PCAT-1). Copy number variability and dysregulation of specific pathways including androgen receptor signaling, PTEN/PAKT and TGF-β continue to play an important role in invasion and metastasis. Given the current challenges for applying prostate cancer genomics to clinical management, this review will incorporate some of the current novel genomic approaches and techniques including systems-based precise pathology platforms, and the role of fluid-based assays, notably, exosomes and circulating tumor cells (liquid biopsy), as tools for future diagnostic-treatment algorithms.Current opinion in urology 03/2014; · 2.50 Impact Factor
Article: ETS fusion genes in prostate cancer.[Show abstract] [Hide abstract]
ABSTRACT: Prostate cancer is very common in elderly men in developed countries. Unravelling of the molecular and biological processes that contribute to tumor development and progressive growth, including its heterogeneity, is a challenging task. The fusion of the genes ERG and TMPRSS2 is the most frequent genomic alteration in prostate cancer. ERG is an oncogene that encodes a member of the family of ETS transcription factors. At lower frequency other members of this gene family are also rearranged and overexpressed in prostate cancer. TMPRSS2 is an androgen-regulated gene that is preferentially expressed in the prostate. Most of the less frequent ETS fusion partners are also androgen-regulated and prostate-specific. During the last few years novel concepts of the process of gene fusion have emerged and initial experimental results explaining the function of the ETS genes ERG and ETV1 in prostate cancer have been published. In this review we focus on the most relevant ETS gene fusions and summarize the current knowledge of the role of ETS transcription factors in prostate cancer. Finally, we discuss the clinical relevance of TMRPSS2-ERG and other ETS gene fusions in prostate cancer.Endocrine Related Cancer 03/2014; · 5.26 Impact Factor