Rational basis for the combination of PCA3 and TMPRSS2:ERG gene fusion for prostate cancer diagnosis.
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.
Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Grégoire
G
Robert
Sander
S
Jannink
Frank
F
Smit
Tilly
T
Aalders
Daphne
D
Hessels
Ruben
R
Cremers
Peter F
PF
Mulders
Jack A
JA
Schalken
D000951:Antigens, Neoplasm / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D050939:Gene Fusion / Q000235:genetics*; D006801:Humans; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D017430:Prostate-Specific Antigen / Q000235:genetics; D011470:Prostatic Hyperplasia / Q000175:diagnosis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; C479341:prostate cancer antigen 3, human; D017430:Prostate-Specific Antigen