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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.
Eric Smith, and
Helen M Palethorpe, and
Andrew R Ruszkiewicz, and
Suzanne Edwards, and
Damien A Leach, and
Tim J Underwood, and
Eleanor F Need, and
Paul A Drew
June 1987,
Molecular and cellular endocrinology,
Eric Smith, and
Helen M Palethorpe, and
Andrew R Ruszkiewicz, and
Suzanne Edwards, and
Damien A Leach, and
Tim J Underwood, and
Eleanor F Need, and
Paul A Drew
July 2005,
Genes, chromosomes & cancer,
Eric Smith, and
Helen M Palethorpe, and
Andrew R Ruszkiewicz, and
Suzanne Edwards, and
Damien A Leach, and
Tim J Underwood, and
Eleanor F Need, and
Paul A Drew
January 2006,
Endocrinology,
Eric Smith, and
Helen M Palethorpe, and
Andrew R Ruszkiewicz, and
Suzanne Edwards, and
Damien A Leach, and
Tim J Underwood, and
Eleanor F Need, and
Paul A Drew
May 2002,
Endocrinology,
Eric Smith, and
Helen M Palethorpe, and
Andrew R Ruszkiewicz, and
Suzanne Edwards, and
Damien A Leach, and
Tim J Underwood, and
Eleanor F Need, and
Paul A Drew
April 2012,
Clinical cancer research : an official journal of the American Association for Cancer Research,
Eric Smith, and
Helen M Palethorpe, and
Andrew R Ruszkiewicz, and
Suzanne Edwards, and
Damien A Leach, and
Tim J Underwood, and
Eleanor F Need, and
Paul A Drew
November 2001,
British journal of haematology,
Eric Smith, and
Helen M Palethorpe, and
Andrew R Ruszkiewicz, and
Suzanne Edwards, and
Damien A Leach, and
Tim J Underwood, and
Eleanor F Need, and
Paul A Drew
December 2018,
Gastroenterology,
Eric Smith, and
Helen M Palethorpe, and
Andrew R Ruszkiewicz, and
Suzanne Edwards, and
Damien A Leach, and
Tim J Underwood, and
Eleanor F Need, and
Paul A Drew
March 2012,
Genes, chromosomes & cancer,
Eric Smith, and
Helen M Palethorpe, and
Andrew R Ruszkiewicz, and
Suzanne Edwards, and
Damien A Leach, and
Tim J Underwood, and
Eleanor F Need, and
Paul A Drew
July 1983,
The Journal of urology,
Eric Smith, and
Helen M Palethorpe, and
Andrew R Ruszkiewicz, and
Suzanne Edwards, and
Damien A Leach, and
Tim J Underwood, and
Eleanor F Need, and
Paul A Drew
January 1974,
Journal of surgical oncology,
