title: Molecular profiling of ETS gene rearrangements in patients with prostate cancer registered in REDEEM clinical trial.
abstract: OBJECTIVE
  Androgen-induced E26 transformation-specific (ETS) gene fusion-positive tumors have been associated with aggressive prostate cancer. The aim is to evaluate the ETS gene rearrangement status on initial biopsy of patients registered in the Reduction by Dutasteride of Clinical Progression Events in Expectant Management trial study and determine if gene fusion status was associated with disease progression.
  
  
  METHODS
  Initial biopsy material from 146 men registered in Reduction by Dutasteride of Clinical Progression Events in Expectant Management trial study treated with dutasteride (73/146, 50%) and as placebo (73/146, 50%) were reviewed, and ERG and SPINK1 immunohistochemistry was performed. ERG- and SPINK1-negative cancer samples were evaluated for ETV1, ETV4, and ETV5 rearrangements by fluorescence in situ hybridization. Frequency of ETS gene aberrations in both groups was correlated with cancer progression including prostate-specific antigen progression, Gleason progression, and progression-free survival by logistic analysis, pairwise differences, and chunk likelihood ratio tests for the genotype groups.
  
  
  CONCLUSIONS
  Of the 146 patients, 99 (67.8%) (placebo, 51; dutasteride, 48) samples displayed the following Gleason patterns: 3+3 = 6 in 80 (54.8%) (placebo, 39; dutasteride, 41), 3+4 = 7 in 18 (12.3%) (placebo, 11; dutasteride, 7), and 4+4 = 8 in 1(0.68%) (placebo, 1). The remaining 47 samples showed atypical glands in 5 (3.4%) (placebo, 2; dutasteride, 3), HGPIN in 9 (6.1%) (placebo, 5; dutasteride, 4), and benign in 33 (22.6%) (placebo, 15; dutasteride, 18). Immunohistochemistry findings were positive for ERG and SPINK1 in 56 (56%) (placebo, 31; dutasteride, 25) and 9 (6.1%) (placebo, 5; dutasteride, 4) cases, respectively. ETV1 and ETV4 rearrangements were noted in 2 cases (1.4%) (placebo, 1; dutasteride, 1) and 1 (0.7%) (placebo, 1) case, respectively. No significant differences in the incidence of prostate cancer molecular aberrations between the groups were observed. There was no evidence that ETS fusion status was associated with disease progression.
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI; Department of Pathology, University of Michigan, Ann Arbor, MI; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI.
authors.forename: Nallasivam
authors.initials: N
authors.lastname: Palanisamy
authors.affiliation: Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI.
authors.forename: Alexi
authors.initials: A
authors.lastname: Tsodikov
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI; Department of Pathology, University of Michigan, Ann Arbor, MI.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI; Department of Pathology, University of Michigan, Ann Arbor, MI.
authors.forename: Khalid
authors.initials: K
authors.lastname: Suleman
authors.affiliation: GlaxoSmithKline, Research Triangle Park, Durham, NC.
authors.forename: Roger
authors.initials: R
authors.lastname: Rittmaster
authors.affiliation: Department of Pathology, University of Colorado, Aurora, CO.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lucia
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI; Department of Pathology, University of Michigan, Ann Arbor, MI; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Department of Urology, University of Michigan, Ann Arbor, MI.
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.affiliation: Princess Margaret Hospital, Toronto, Ontario, Canada.
authors.forename: Neil
authors.initials: N
authors.lastname: Fleshner
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI; Department of Pathology, University of Michigan, Ann Arbor, MI; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI. Electronic address: lkunju@med.umich.edu.
authors.forename: Lakshmi P
authors.initials: LP
authors.lastname: Kunju
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000627:therapeutic use; D017500:Adenovirus E1A Proteins / Q000235:genetics; D001706:Biopsy; D022202:Chromosomes, Artificial, Bacterial; D002986:Clinical Trials as Topic; D004268:DNA-Binding Proteins / Q000235:genetics; D018450:Disease Progression; D000068538:Dutasteride / Q000627:therapeutic use; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000628:therapy*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors / Q000235:genetics
chemical_list: D058891:5-alpha Reductase Inhibitors; D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; C095239:ETV1 protein, human; C079853:ETV4 protein, human; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D000068538:Dutasteride
keywords: Fluorescence in situ hybridization; Gene fusion; Immunohistochemistry; Prostate cancer; REDEEM trial