Evaluation of the ETS-Related Gene mRNA in Urine for the Detection of Prostate Cancer

Abstract

Purpose: Prevalent gene fusions in prostate cancer involve androgen-regulated promoters (primarily TMPRSS2) and ETS transcription factors (predominantly ETS-regulated gene (ERG)], which result in tumor selective overexpression of ERG in two thirds of patients. Because diverse genomic fusion events lead to ERG overexpression in prostate cancer, we reasoned that it may be more practical to capture such alterations using an assay targeting ERG sequences retained in such gene fusions. This study evaluates the potential of an assay quantitating ERG mRNA in post-digital rectal exam (DRE) urine for improving prostate cancer detection.Experimental Design: Patients scheduled to undergo transrectal ultrasound-guided needle biopsy of the prostate were prospectively enrolled. On the day of biopsy, patients provided a urine sample immediately following a DRE. Urine ERG mRNA was measured and normalized to urine prostate-specific antigen (PSA) mRNA using the DTS 400 system. Demographic traits, clinical characteristics and biopsy results were analyzed for association with urine ERG score.Results: The study was conducted on 237 patients. Prostate cancer was shown on biopsy in 40.9% of study subjects. A higher urine ERG score associated significantly with malignancy on biopsy (P = 0.0145), but not with clinical stage or Gleason score. Urine ERG score performed best in Caucasians and in men with a PSA of ≤4 ng/mL (area under the curve = 0.8).Conclusions: A higher urine ERG score in post-DRE urine is associated with the diagnosis of prostate cancer on biopsy. Urine ERG score performed particularly well in men with a PSA of ≤4.0 ng/mL, a segment of the screening population in which further diagnostic markers are needed to determine in whom biopsy should be done. Clin Cancer Res; 16(5); 1572-6. ©2010 AACR.

Predominance of ERG-negative high-grade prostate cancers in African American men

“…The highly prevalent ERG fusions, present in over half of all CaPs in Western countries, result in androgen-dependent and prostate tumor-specific expression of the ERG fusion transcripts and a near-full-length ERG protein with a 32-amino acid deletion at the amino terminus (6)(7)(8)(9). Evaluations of the ERG alterations at the genomic, transcriptional and protein levels have continued to suggest lower frequencies of ERG in AA CaP in comparison to CA CaP (10)(11)(12)(13). Almost complete concordance between the detection of ERG gene fusions by fluorescence in situ hybridization and ERG protein detection by immunohistochemistry (IHC), has significantly accelerated the evaluation of the ERG protein as the surrogate of this common CaP genome alteration in pathological specimens (14)(15)(16)(17).…”

Biomarkers of Aggressiveness in Prostate Cancer

“…Of note, the TMPRSSE:ERG fusion has potential for noninvasive prognosis of prostate cancer. Although RNA-based urinary tests demonstrate in general a high specificity and sensitivity to detect prostate cancer, no significant relationship was found between the presence of fusion transcripts and Gleason score or clinical stage Rice et al, 2010).…”

319 Using gene expression from urine sediment to diagnose prostate cancer: Development of a new multiplex mRNA urine test and validation of current biomarkers

“…We used as endogenous control the mean Cq value of KLK2 and KLK3, which allowed us to normalize the prostate epithelial cell content in the collected urine sample [4]. Most of the studies seeking urinary transcripts for PCa diagnosis have used KLK3 as a prostate-specific endogenous control [4,18,19]. In this study, to minimize the possibility of erroneous relative gene expression quantification, we also selected KLK2 as a second prostatespecific endogenous control since its expression level is highly correlated with KLK3 [20].…”