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Type: Journal article
Title: Androgen receptor and androgen-responsive gene FKBP5 are independent prognostic indicators for esophageal adenocarcinoma
Author: Smith, E.
Palethorpe, H.
Ruszkiewicz, A.
Edwards, S.
Leach, D.
Underwood, T.
Need, E.
Drew, P.
Citation: Digestive Diseases and Sciences, 2016; 61(2):433-443
Publisher: Springer
Issue Date: 2016
ISSN: 0163-2116
Statement of
Eric Smith, Helen M. Palethorpe, Andrew R. Ruszkiewicz, Suzanne Edwards, Damien A. Leach, Tim J. Underwood, Eleanor F. Need, Paul A. Drew
Abstract: BACKGROUND: Esophageal adenocarcinoma is a male-dominant disease, but the role of androgens is unclear. AIMS: 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. CONCLUSION: Nuclear AR and expression of FKBP5 is associated with decreased survival in esophageal adenocarcinoma.
Keywords: Adenocarcinoma of the esophagus
Androgen receptors
FK506-binding protein 5
Rights: © Springer Science+Business Media New York 2015
DOI: 10.1007/s10620-015-3909-0
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