期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 3, 期 94, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.3001970
关键词
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资金
- Gen-Probe Inc.
- Early Detection Research Network [U01 CA111275, U01 CA113913]
- NIH SPORE [P50 CA69568]
- Prostate Cancer Foundation
- Burroughs Wellcome Fund
- Doris Duke Foundation
- [R01 CA132874]
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.
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