TY - JOUR
T1 - Androgen receptor and androgen-responsive gene FKBP5 are independent prognostic indicators for esophageal adenocarcinoma
AU - Smith, Eric
AU - Palethorpe, Helen
AU - Ruszkiewicz, Andrew R
AU - Edwards, Suzanne
AU - Leach, Damien
AU - Underwood, Timothy
AU - Need, Eleanor
AU - Drew, Paul
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
KW - Adenocarcinoma of the esophagus
KW - Androgen receptors
KW - FK506-binding protein 5
KW - Prognosis
KW - Steroids
UR - http://www.scopus.com/inward/record.url?scp=84944562149&partnerID=8YFLogxK
U2 - 10.1007/s10620-015-3909-0
DO - 10.1007/s10620-015-3909-0
M3 - Article
SN - 0163-2116
VL - 61
SP - 433
EP - 443
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
IS - 2
ER -