title: Urine TMPRSS2:ERG fusion transcript stratifies prostate cancer risk in men with elevated serum PSA.
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.affiliation: Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tomlins
authors.forename: Sheila M J
authors.initials: SM
authors.lastname: Aubin
authors.forename: Javed
authors.initials: J
authors.lastname: Siddiqui
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lonigro
authors.forename: Laurie
authors.initials: L
authors.lastname: Sefton-Miller
authors.forename: Siobhan
authors.initials: S
authors.lastname: Miick
authors.forename: Sarah
authors.initials: S
authors.lastname: Williamsen
authors.forename: Petrea
authors.initials: P
authors.lastname: Hodge
authors.forename: Jessica
authors.initials: J
authors.lastname: Meinke
authors.forename: Amy
authors.initials: A
authors.lastname: Blase
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Penabella
authors.forename: John R
authors.initials: JR
authors.lastname: Day
authors.forename: Radhika
authors.initials: R
authors.lastname: Varambally
authors.forename: Bo
authors.initials: B
authors.lastname: Han
authors.forename: David
authors.initials: D
authors.lastname: Wood
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Martin G
authors.initials: MG
authors.lastname: Sanda
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Rhodes
authors.forename: Brent
authors.initials: B
authors.lastname: Hollenbeck
authors.forename: Kyoko
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Silberstein
authors.forename: Yves
authors.initials: Y
authors.lastname: Fradet
authors.forename: James B
authors.initials: JB
authors.lastname: Amberson
authors.forename: Stephanie
authors.initials: S
authors.lastname: Meyers
authors.forename: Nallasivam
authors.initials: N
authors.lastname: Palanisamy
authors.forename: Harry
authors.initials: H
authors.lastname: Rittenhouse
authors.forename: John T
authors.initials: JT
authors.lastname: Wei
authors.forename: Jack
authors.initials: J
authors.lastname: Groskopf
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D015331:Cohort Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000652:urine; D012333:RNA, Messenger / Q000652:urine*; D018570:Risk Assessment
chemical_list: D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C515553:TMPRSS2-ERG fusion protein, human; D017430:Prostate-Specific Antigen