Rational basis for the combination of PCA3 and TMPRSS2:ERG gene fusion for prostate cancer diagnosis

Prostate. 2013 Jan;73(2):113-20. doi: 10.1002/pros.22546. Epub 2012 Jun 5.


Background: The prostate cancer gene 3 (PCA3) and TMPRSS2:ERG gene fusion are promising prostate cancer (PCa) specific biomarkers. Our aim was to simultaneously quantify the expression levels of PCA3 and TMPRSS2:ERG in a panel of benign prostatic hyperplasia (BPH), normal prostate adjacent to PCa (NP) and PCa tissue samples, to provide a rational basis for the understanding of the false-positive and false-negative results of the urine assays.

Methods: The tissue samples were carefully histopathologically characterized to obtain homogeneous groups. The mRNA was isolated, transcribed into cDNA and the relative expressions of PCA3 and TMPRSS2:ERG were measured using a quantitative real-time polymerase chain reaction. The expression levels of PCA3 and TMPRSS2:ERG were compared between the different groups.

Results: We included 48 BPH, 32 NP, and 48 PCa. The PCA3 expression levels progressively increased from BPH to NP (3 times) and finally to PCa (30 times). There were one false-positive sample and seven false-negative samples. The TMPRSS2:ERG gene fusion was found in 8.3% of the BPH, 15.6% of the NP, and 50% of the PCa samples. The use of TMPRSS2:ERG in the PCA3 negative cases allowed diagnosis of four of the seven false-negative samples and added one false-positive, but we had to define a cut-off value to avoid eight false-positive results.

Conclusions: Considering tissue expression of the markers, most of the false-negative results of the PCA3 test were corrected by TMPRSS2:ERG (57%) and the combination of both had a higher sensitivity for PCa diagnosis. Some of the control samples did express TMPRSS2:ERG and a cut-off value had to be defined to avoid false-positive results.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics*
  • Biomarkers, Tumor / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Fusion / genetics*
  • Humans
  • Male
  • Oncogene Proteins, Fusion / genetics*
  • Prostate-Specific Antigen / genetics
  • Prostatic Hyperplasia / diagnosis
  • Prostatic Hyperplasia / genetics
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / genetics*
  • Up-Regulation / genetics


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Oncogene Proteins, Fusion
  • TMPRSS2-ERG fusion protein, human
  • prostate cancer antigen 3, human
  • Prostate-Specific Antigen