Digestive Diseases and Sciences

, Volume 61, Issue 2, pp 433–443 | Cite as

Androgen Receptor and Androgen-Responsive Gene FKBP5 Are Independent Prognostic Indicators for Esophageal Adenocarcinoma

  • Eric Smith
  • Helen M. Palethorpe
  • Andrew R. Ruszkiewicz
  • Suzanne Edwards
  • Damien A. Leach
  • Tim J. Underwood
  • Eleanor F. Need
  • Paul A. Drew
Original Article



Esophageal adenocarcinoma is a male-dominant disease, but the role of androgens is unclear.


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.


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.


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.


Nuclear AR and expression of FKBP5 is associated with decreased survival in esophageal adenocarcinoma.


Adenocarcinoma of the esophagus Androgen receptors FK506-binding protein 5 Steroids Prognosis 

Supplementary material

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Supplementary material 1 (DOCX 78 kb)
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Supplementary material 2 (DOCX 101 kb)
10620_2015_3909_MOESM3_ESM.docx (95 kb)
Supplementary material 3 (DOCX 95 kb)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Solid Cancer Regulation Group, Discipline of Surgery, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth HospitalThe University of AdelaideWoodville SouthAustralia
  2. 2.Gastroenterology Research LaboratorySA PathologyAdelaideAustralia
  3. 3.Data Management and Analysis Centre, Royal Adelaide HospitalThe University of AdelaideAdelaideAustralia
  4. 4.Cancer Biology Group, Discipline of Surgery, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth HospitalThe University of AdelaideWoodville SouthAustralia
  5. 5.Cancer Sciences Unit, Somers Cancer Research Building, Southampton General HospitalUniversity of SouthamptonSouthamptonUK
  6. 6.Breast Biology and Cancer Unit, Discipline of Surgery, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth HospitalThe University of AdelaideWoodville SouthAustralia
  7. 7.School of Nursing and MidwiferyFlinders UniversityAdelaideAustralia

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