Abstract

More than 1,000,000 men undergo prostate biopsy each year in the United States, most for "elevated" serum prostate-specific antigen (PSA). Given the lack of specificity and unclear mortality benefit of PSA testing, methods to individualize management of elevated PSA are needed. Greater than 50% of PSA-screened prostate cancers harbor fusions between the transmembrane protease, serine 2 (TMPRSS2) and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) genes. Here, we report a clinical-grade, transcription-mediated amplification assay to risk stratify and detect prostate cancer noninvasively in urine. The TMPRSS2:ERG fusion transcript was quantitatively measured in prospectively collected whole urine from 1312 men at multiple centers. Urine TMPRSS2:ERG was associated with indicators of clinically significant cancer at biopsy and prostatectomy, including tumor size, high Gleason score at prostatectomy, and upgrading of Gleason grade at prostatectomy. TMPRSS2:ERG, in combination with urine prostate cancer antigen 3 (PCA3), improved the performance of the multivariate Prostate Cancer Prevention Trial risk calculator in predicting cancer on biopsy. In the biopsy cohorts, men in the highest and lowest of three TMPRSS2:ERG+PCA3 score groups had markedly different rates of cancer, clinically significant cancer by Epstein criteria, and high-grade cancer on biopsy. Our results demonstrate that urine TMPRSS2:ERG, in combination with urine PCA3, enhances the utility of serum PSA for predicting prostate cancer risk and clinically relevant cancer on biopsy.

Authors

• Amberson JB
• Aubin SM
• Blase A
• Chinnaiyan AM
• Day JR
• Fradet Y
• Groskopf J
• Han B
• Hodge P
• Hollenbeck B
• Lonigro RJ
• Meinke J
• Meyers S
• Miick S
• Palanisamy N
• Penabella Y
• Rhodes DR
• Rittenhouse H
• Rubin MA
• Sakamoto K
• Sanda MG
• Sefton-Miller L
• Siddiqui J
• Silberstein JL
• Tomlins SA
• Varambally R
• Wang L
• Wei JT
• Williamsen S
• Wood D

PubMed ID

Appears In

Sci Transl Med, 2011, 3 (94)