Detection of TMPRSS2-ERG fusion transcripts and prostate cancer antigen 3 in urinary sediments may improve diagnosis of prostate cancer.
OBJECTIVE
Early detection of prostate cancer can increase the curative success rate for prostate cancer. We studied the diagnostic usefulness of TMPRSS2-ERG fusion transcripts as well as the combination of prostate cancer antigen 3 (PCA3) RNA and TMPRSS2-ERG fusion transcripts in urinary sediments after digital rectal examination (DRE).


METHODS
A total of 78 men with prostate cancer-positive biopsies and 30 men with prostate cancer-negative biopsies were included in this study. After DRE, the first voided urine was collected, and urinary sediments were obtained. We used semiquantitative reverse transcription-PCR (RT-PCR) analysis followed by Southern blot hybridization with a radiolabeled probe for the detection TMPRSS2-ERG fusion transcripts in these urinary sediments. A quantitative RT-PCR assay for PCA3 was used to determine the PCA3 score in the same sediments.


RESULTS
TMPRSS2-ERG fusion transcripts can be detected in the urine after DRE with a sensitivity of 37%. In this cohort of patients, the PCA3-based assay had a sensitivity of 62%. When both markers were combined, the sensitivity increased to 73%. Especially in the cohort of men with persistently elevated serum prostate-specific antigen levels and history of negative biopsies, the high positive predictive value of 94% of TMPRSS2-ERG fusion transcripts could give a better indication which patients require repeat biopsies.


CONCLUSIONS
In this report, we used for the first time the combination of the prostate cancer-specific biomarkers TMPRSS2-ERG and PCA3, which significantly improves the sensitivity for prostate cancer diagnosis.
Hessels
Daphne
D
Experimental Urology, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
Smit
Frank P
FP
Verhaegh
Gerald W
GW
Witjes
J Alfred
JA
Cornel
Erik B
EB
Schalken
Jack A
JA
D000951:Antigens, Neoplasm / Q000652:urine*; D014408:Biomarkers, Tumor; D006801:Humans; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000652:urine; D012333:RNA, Messenger / Q000652:urine*; D020133:Reverse Transcriptase Polymerase Chain Reaction