title: Androgen receptor expression is associated with prostate cancer-specific survival in castrate patients with metastatic disease.
abstract: OBJECTIVE
  To investigate whether baseline (before treatment) clinical variables and tumour specimen characteristics (including the androgen receptor, AR) from patients with castrate-resistant metastatic prostate cancer can be used to predict the time to prostate cancer-specific mortality and overall survival, as AR levels in prostate cancer have been associated with disease progression, including prostate-specific antigen (PSA) recurrence and systemic metastasis.
  
  
  METHODS
  Haematoxylin and eosin (H&E) slides/blocks and outcome data from a 104 castrate patients with metastatic disease (43 prostatectomy and 61 prostate needle biopsy samples), were independently reviewed; H&E morphometry and quantitative immunofluorescence were used to assess the samples. Sections were analysed with a multiplex quantitative immunofluorescence (IF) assay for cytokeratin-18 (epithelial cells), 4',6-diamidino-2-phenylindole (nuclei), p63/high molecular weight keratin (basal cells), AR and alpha-methyl CoA-racemase. Images were acquired with spectral imaging software and processed for quantification with IF algorithms.
  
  
  RESULTS
  The median follow-up was 12 years from diagnosis; 49 men (47%) baseline PSA levels of > or = 20 ng/mL, 55 (53%) had a Gleason sum of 8, 63 (60%) died from the disease and 40% were alive (censored). In all, 66 patients had evaluable IF features, and the association with outcome was evaluated by univariate Cox modelling and support-vector regression. PSA was the only clinical variable associated with outcome (concordance index, CoI, 0.41; P < 0.05, log-rank test). The amount of AR present within tumour nuclei (regardless of tissue provenance and primary treatment) significantly correlated with a greater risk of a shorter time to prostate cancer-specific mortality (CoI 0.36; P < 0.05 log-rank test). There were no H&E features that correlated with mortality.
  
  
  CONCLUSIONS
  By univariate analysis, increased nuclear AR expression in either the diagnostic biopsy and/or radical prostatectomy specimen, from patients with advanced disease, was associated with a reduced time to prostate cancer-specific mortality.
authors.affiliation: Aureon Laboratories, Yonkers, New York, NY, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Donovan
authors.forename: Iman
authors.initials: I
authors.lastname: Osman
authors.forename: Faisal M
authors.initials: FM
authors.lastname: Khan
authors.forename: Yevgen
authors.initials: Y
authors.lastname: Vengrenyuk
authors.forename: Paola
authors.initials: P
authors.lastname: Capodieci
authors.forename: Michael
authors.initials: M
authors.lastname: Koscuiszka
authors.forename: Aseem
authors.initials: A
authors.lastname: Anand
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordon-Cardo
authors.forename: Jose
authors.initials: J
authors.lastname: Costa
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
mesh_terms: D000368:Aged; D000728:Androgens / Q000378:metabolism*; D004812:Epidemiologic Methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D009376:Neoplasms, Hormone-Dependent / Q000401:mortality* / Q000473:pathology; D009919:Orchiectomy; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000401:mortality* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000728:Androgens; D009363:Neoplasm Proteins; D011944:Receptors, Androgen