title: Higher tumor to benign ratio of the androgen receptor mRNA expression associates with prostate cancer progression after radical prostatectomy.
abstract: OBJECTIVE
  Alterations of androgen receptor (AR) functions caused by overexpression, amplification, or mutation have been described in a significant subset of advanced prostate cancer (CaP). Because AR mutations or amplification are rare in early stage CaP, we hypothesized that altered AR expression in prostate tumor cells may provide a prognostic indicator of disease progression.
  
  
  METHODS
  RNA from laser capture microdissected (LCM) tumor and benign epithelial cells from radical prostatectomy specimens of 115 hormone-naive patients were studied. Expression of AR and GAPDH genes were measured by duplex quantitative real-time polymerase chain reaction (RT-PCR) in 230 specimens. A ratio of the expression of AR gene, normalized to GAPDH gene expression in the same specimens, was compared in tumor and benign epithelial cells (tumor-to-benign ratio) and correlated with clinicopathologic features.
  
  
  RESULTS
  Paired t test analysis revealed a 62% lower AR expression in tumor tissue compared with benign tissue (P = 0.0005). However, multivariate Cox proportional hazards regression analysis of time to PSA recurrence revealed that higher tumor cell associated AR expression (continuous, log-transformed), significantly increases odds of prostate-specific antigen (PSA) recurrence (P = 0.0139) when controlling for age at surgery, race, time from diagnosis to surgery, risk stratification, pathologic T stage, Gleason sum, and margin status.
  
  
  CONCLUSIONS
  Quantitative determination of AR gene expression levels in prostate epithelial cells may be useful for predicting PSA recurrence. This study supports the accumulating data suggesting that gain of AR function may contribute to CaP progression.
authors.affiliation: Center for Prostate Disease Research, Department of Surgery, and Unites States Military Cancer Institute, Uniformed Services University, Rockville, Maryland 20852, USA.
authors.forename: Inger L
authors.initials: IL
authors.lastname: Rosner
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Ravindranath
authors.forename: Bungo
authors.initials: B
authors.lastname: Furusato
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Chen
authors.forename: Chunling
authors.initials: C
authors.lastname: Gao
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cullen
authors.forename: Isabell A
authors.initials: IA
authors.lastname: Sesterhenn
authors.forename: David G
authors.initials: DG
authors.lastname: McLeod
authors.forename: Shiv
authors.initials: S
authors.lastname: Srivastava
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Petrovics
mesh_terms: D000328:Adult; D018450:Disease Progression; D015870:Gene Expression; D006801:Humans; D008297:Male; D011379:Prognosis; D011467:Prostate / Q000378:metabolism*; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000601:surgery; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen