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. 2011 Aug 3;3(94):94ra72.
doi: 10.1126/scitranslmed.3001970.

Urine TMPRSS2:ERG fusion transcript stratifies prostate cancer risk in men with elevated serum PSA

Scott A Tomlins  1 , Sheila M J Aubin, Javed Siddiqui, Robert J Lonigro, Laurie Sefton-Miller, Siobhan Miick, Sarah Williamsen, Petrea Hodge, Jessica Meinke, Amy Blase, Yvonne Penabella, John R Day, Radhika Varambally, Bo Han, David Wood, Lei Wang, Martin G Sanda, Mark A Rubin, Daniel R Rhodes, Brent Hollenbeck, Kyoko Sakamoto, Jonathan L Silberstein, Yves Fradet, James B Amberson, Stephanie Meyers, Nallasivam Palanisamy, Harry Rittenhouse, John T Wei, Jack Groskopf, Arul M Chinnaiyan
Affiliations

Urine TMPRSS2:ERG fusion transcript stratifies prostate cancer risk in men with elevated serum PSA

Scott A Tomlins et al. Sci Transl Med. .

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.

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Conflict of interest statement

Competing interests: The University of Michigan and Brigham and Women’s Hospital have been issued a patent on the detection of ETS gene fusions in prostate cancer, on which S.A.T., M.A.R., D.R.R., and A.M.C. are listed as coinventors. The diagnostic field of use has been licensed to Gen-Probe. A.M.C. and J.T.W. have served as consultants for Gen-Probe. Gen-Probe has provided material support for a clinical trial evaluating PCA3, on which J.T.W. is the primary investigator. Y.F. is cofounder of Diagnocure, which licensed diagnostic rights to the PCA3 gene to Gen-Probe. J.S. and M.A.R. have received honoraria from Gen-Probe. M.G.S. has received research funding from Beckman-Coulter and Source-MDx. S.M.J.A., S. Miick, S.W., P.H., J.M., J.R.D., A.B., Y.P., H.R., and J.G. are employees of Gen-Probe. The remaining authors declare no conflicts of interest.

Figures

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