title: Androgen Receptor and Androgen-Responsive Gene FKBP5 Are  Independent Prognostic Indicators for Esophageal  Adenocarcinoma.
abstract: BACKGROUND
  Esophageal adenocarcinoma is a male-dominant disease, but the role of androgens is unclear.
  
  
  OBJECTIVE
  To examine the expression and clinical correlates of the androgen receptor (AR) and the androgen-responsive gene FK506-binding protein 5 (FKBP5) in esophageal adenocarcinoma.
  
  
  METHODS
  Expression of AR and FKBP5 was determined by immunohistochemistry. The effect of the AR ligand 5α-dihydrotestosterone (DHT) on the expression of a panel of androgen-responsive genes was measured in AR-positive and AR-negative esophageal adenocarcinoma cell lines. Correlations in expression between androgen-responsive genes were analyzed in an independent cohort of esophageal adenocarcinoma tissues.
  
  
  RESULTS
  There was AR staining in 75 of 77 cases (97 %), and FKBP5 staining in 49 (64 %), all of which had nuclear AR. Nuclear AR with FKBP5 expression was associated with decreased median survival (451 vs. 2800 days) and was an independent prognostic indicator (HR 2.894, 95 % CI 1.396–6.002, p = 0.0043) in multivariable Cox proportional hazards models. DHT induced a significant increase in expression of the androgen-responsive genes FKBP5, HMOX1, FBXO32, VEGFA, WNT5A, and KLK3 only in AR-positive cells in vitro. Significant correlations in expression were observed between these androgen-responsive genes in an independent cohort of esophageal adenocarcinoma tissues.
  
  
  CONCLUSIONS
  Nuclear AR and expression of FKBP5 is associated with decreased survival in esophageal adenocarcinoma.
authors.forename: Eric
authors.initials: E
authors.lastname: Smith
authors.forename: Helen M
authors.initials: HM
authors.lastname: Palethorpe
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Ruszkiewicz
authors.forename: Suzanne
authors.initials: S
authors.lastname: Edwards
authors.forename: Damien A
authors.initials: DA
authors.lastname: Leach
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Underwood
authors.forename: Eleanor F
authors.initials: EF
authors.lastname: Need
authors.forename: Paul A
authors.initials: PA
authors.lastname: Drew
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D011379:Prognosis; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099159:Tacrolimus Binding Protein 5
chemical_list: D011944:Receptors, Androgen; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C410798:AR protein, human