Androgen receptor and androgen-responsive gene FKBP5 are independent prognostic indicators for esophageal adenocarcinoma

Eric Smith, Helen Palethorpe, Andrew R Ruszkiewicz, Suzanne Edwards, Damien Leach, Timothy Underwood, Eleanor Need, Paul Drew

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    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.

    Original languageEnglish
    Pages (from-to)433-443
    Number of pages11
    JournalDigestive Diseases and Sciences
    Volume61
    Issue number2
    DOIs
    Publication statusPublished - 1 Feb 2016

    Keywords

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

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    Smith, E., Palethorpe, H., Ruszkiewicz, A. R., Edwards, S., Leach, D., Underwood, T., Need, E., & Drew, P. (2016). Androgen receptor and androgen-responsive gene FKBP5 are independent prognostic indicators for esophageal adenocarcinoma. Digestive Diseases and Sciences, 61(2), 433-443. https://doi.org/10.1007/s10620-015-3909-0