Detection of TMPRSS2-ERG Fusion Transcripts and Prostate Cancer Antigen 3 in Urinary Sediments May Improve Diagnosis of Prostate Cancer

• Published in: Clinical cancer research Vol. 13; no. 17; pp. 5103 - 5108
• Main Authors: HESSELS, Daphne, SMIT, Frank P, VERHAEGH, Gerald W, WITJES, J. Alfred, CORNET, Erik B, SCHALKEN, Jack A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.09.2007
• Subjects: Antigens, Neoplasm - urine; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor; gene fusions; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Nephrology. Urinary tract diseases; Oncogene Proteins, Fusion - genetics; PCA3; Pharmacology. Drug treatments; Prognosis; prostate cancer; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - mortality; Prostatic Neoplasms - urine; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - urine; TMPRSS2-ERG; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; urine; Antigen; Urinary system disease; Prostate disease; C-Onc gene; Malignant tumor; Diagnosis; Detection; Male genital diseases; Prostate cancer; Hybrid gene; Protooncogene
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-07-0700

Purpose: 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). Experimental Design: 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. Conclusion: 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.