title: Transcript levels of androgen receptor variant AR-V1 or AR-V7 do not predict recurrence in patients with prostate cancer at indeterminate risk for progression.
abstract: OBJECTIVE
  AR-V7, a ligand independent splice variant of androgen receptor, may support the growth of castration resistant prostate cancer and have prognostic value. Another variant, AR-V1, interferes with AR-V7 activity. We investigated whether AR-V7 or V1 expression would predict biochemical recurrence in men at indeterminate (about 50%) risk for progression following radical prostatectomy.
  
  
  METHODS
  AR-V7 and V1 transcripts in a mixed grade cohort of 53 men in whom cancer contained 30% to 70% Gleason grade 4/5 and in a grade 3 only cohort of 52 were measured using a branched chain DNA assay. Spearman rank correlations of the transcripts, and histomorphological and clinical variables were determined. AR-V7 and V1 levels were assessed as determinants of recurrence in the mixed grade cohort by logistic regression and survival analysis. The impact of TMPRSS2-ERG gene fusion on prognosis was also evaluated.
  
  
  RESULTS
  Neither AR-V7 nor V1 levels in grade 3 or 4/5 cancer in the mixed grade cohort were associated with recurrence or time to recurrence. However, AR-V7 and V1 inversely correlated with serum prostate specific antigen and positively correlated with age. The AR-V1 level in grade 3 cancer in the grade 3 only cohort was higher than in grade 3 or grade 4/5 components of mixed grade cancer. TMPRSS2-ERG fusion was not associated with AR-V7, AR-V1 or recurrence but it was associated with the percent of grade 4/5 cancer.
  
  
  CONCLUSIONS
  The AR-V1 or V7 transcript level does not predict recurrence in patients with high grade prostate cancer at indeterminate risk for progression. Grade 3 cancer in mixed grade tumors may differ from 100% grade 3 cancer, at least in AR-V1 expression.
authors.affiliation: Department of Urology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Zhao
authors.forename: Marc A
authors.initials: MA
authors.lastname: Coram
authors.forename: Rosalie
authors.initials: R
authors.lastname: Nolley
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Reese
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Young
authors.forename: Donna M
authors.initials: DM
authors.lastname: Peehl
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D011379:Prognosis; D011467:Prostate / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery; D011944:Receptors, Androgen / Q000378:metabolism*; D012008:Recurrence; D012306:Risk
chemical_list: C410798:AR protein, human; D014408:Biomarkers, Tumor; D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen