title: Expression of androgen receptor in non-muscle-invasive bladder cancer predicts the preventive effect of androgen deprivation therapy on tumor recurrence.
abstract: Our recent retrospective study revealed a significantly reduced risk of bladder cancer (BC) recurrence in men who received androgen deprivation therapy (ADT) for their prostate cancer. However, whether androgen receptor (AR) signals contributed to the preventive effect of ADT remained unclear because ADT could reduce serum estrogens as well. The purpose of this study is to investigate the associations between the expression of AR/estrogen receptors (ERs) and BC recurrence in patients treated with ADT. We immunohistochemically stained 72 BCs and 42 corresponding normal urothelial tissues. AR/ERα/ERβ were positive in 44(61%)/22(31%)/39(54%) tumors and 35(83%)/24(57%)/34(81%) corresponding normal urothelial tissues, respectively. There were no statistically significant correlations between AR/ERα/ERβ expression and clinicopathological features of BC. With a median follow-up of 31.3 months, 12 (43%) of 28 patients with AR-negative tumor versus 11 (23%) of 44 patients with AR-positive tumor experienced BC recurrence. Thus, patients with AR-positive tumor had a significantly lower risk of BC recurrence (P=0.031), compared with those with AR-negative tumor. Meanwhile, the expression of ERα/ERβ in tumors and that of AR/ERα/ERβ in normal urothelial tissues were not significantly correlated with BC recurrence. A multivariate analysis revealed AR positivity in tumors as an independent prognosticator (hazard ratio: 0.27; 95% confidence interval: 0.11-0.67) for BC recurrence. These results indicate that ADT prevents BC recurrence via the AR pathway, but not via the ERα/ERβ pathways.
authors.affiliation: Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.|Department of Urology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Izumi
authors.affiliation: Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Departments of Pathology and Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyamoto
authors.affiliation: Department of Urology, Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Miyoshi
authors.affiliation: Department of Urology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Ota
authors.affiliation: Department of Urology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Moriyama
authors.affiliation: Department of Urology, International Goodwill Hospital, Yokohama, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Murai
authors.affiliation: Department of Pathology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Pathology, Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Inayama
authors.affiliation: Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yao
authors.affiliation: Department of Urology, Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: Hiroji
authors.initials: H
authors.lastname: Uemura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D018450:Disease Progression; D047628:Estrogen Receptor alpha / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011944:Receptors, Androgen / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism*
chemical_list: C410798:AR protein, human; D000726:Androgen Antagonists; D014408:Biomarkers, Tumor; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D011944:Receptors, Androgen
keywords: androgen deprivation therapy; androgen receptor; bladder cancer; recurrence