Urine TMPRSS2:ERG Fusion Transcript Stratifies Prostate Cancer Risk in Men with Elevated Serum PSA

作者：Tomlins Scott A; Aubin Sheila M J; Siddiqui Javed; Lonigro Robert J; Sefton Miller Laurie; Miick Siobhan; Williamsen Sarah; Hodge Petrea; Meinke Jessica; Blase Amy; Penabella Yvonne; Day John R; Varambally Radhika; Han Bo; Wood David; Wang Lei; Sanda Martin G; Rubin Mark A; Rhodes Daniel R; Hollenbeck Brent; Sakamoto Kyoko; Silberstein Jonathan L; Fradet Yves; Amberson James B; Meyers Stephanie; Palanisamy Nallasivam; Rittenhouse Harry; Wei John T

来源：Science Translational Medicine, 2011, 3(94): 94ra72.

DOI：10.1126/scitranslmed.3001970

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.

• 出版日期2011-8-3