Distinct ERG rearrangement prevalence in prostate cancer: higher frequency in young age and in low PSA prostate cancer

Prostate Cancer Prostatic Dis. 2013 Jun;16(2):132-8. doi: 10.1038/pcan.2013.4. Epub 2013 Feb 5.

Abstract

Background: The TMPRSS2-ERG gene fusion resulting in ERG overexpression has been found in around 50% of prostate cancers (PCa) and is a very early event in tumorigenesis. Most studies have reported on selected surgical cohorts with inconsistent results. We hypothesized that ERG gene rearrangements impact tumor development and investigated the frequency of ERG overexpression in the context of clinicopathological tumor characteristics.

Methods: ERG overexpression (ERG+ or ERG-) was determined by immunohistochemistry (IHC) in 1039 radical prostatectomy (RP) tumors and association with PSA, D'Amico risk score, histopathology, biochemical recurrence, body mass index and age of PCa cases was analyzed.

Results: ERG+ was associated with younger age at diagnosis (P<0.0001), lower serum PSA (P=0.002) and lower prostate volume (PV) (P=0.001). It was most frequent in the youngest age quartile (≤55 years, 63.9% ERG+) and decreased constantly with increasing age to 40.8% in the oldest age quartile (≥67 years, P<0.0001). In the PSA range <4 ng ml(-1) the frequency of ERG positivity was 60.2% compared with 47.5 and 49.1% in the PSA ranges 4-10 and ≥10 ng ml(-1), respectively. In the first age quartile, ERG+ patients had lower median serum PSA and fPSA% and smaller PV. In the highest age quartile tumor volume (TV) was increased. Similar differences were observed in the low PSA range. Multivariate analysis identified the first age quartile as a predictor for ERG status (odds ratios (OR) 2.05, P=0.007). No association was found with the D'Amico progression risk score and with biochemical tumor recurrence.

Conclusions: ERG+ tumors manifest clinically at lower PSA levels and their prevalence is age dependent. This suggests acceleration of tumor development by ERG overexpression that results in earlier tumor detection in young patients. Long-term results are warranted to determine the impact of ERG overexpression on disease outcome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Distribution
  • Aged
  • Aged, 80 and over
  • Body Mass Index
  • Early Detection of Cancer
  • Gene Expression
  • Humans
  • Kallikreins / blood
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Oncogene Proteins, Fusion / biosynthesis
  • Oncogene Proteins, Fusion / genetics
  • Proportional Hazards Models
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Sensitivity and Specificity
  • Trans-Activators / biosynthesis
  • Trans-Activators / genetics*
  • Transcriptional Regulator ERG
  • Translocation, Genetic

Substances

  • ERG protein, human
  • Oncogene Proteins, Fusion
  • TMPRSS2-ERG fusion protein, human
  • Trans-Activators
  • Transcriptional Regulator ERG
  • Kallikreins
  • kallikrein-related peptidase 3, human
  • Prostate-Specific Antigen