Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/96352
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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 1573-2568 |
Statement of Responsibility: | 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 Prognosis Steroids |
Rights: | © Springer Science+Business Media New York 2015 |
DOI: | 10.1007/s10620-015-3909-0 |
Published version: | http://dx.doi.org/10.1007/s10620-015-3909-0 |
Appears in Collections: | Aurora harvest 3 Medicine publications |
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hdl_96352.pdf | Accepted Version | 381.29 kB | Adobe PDF | View/Open |
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