Expression of androgen receptor in non-muscle-invasive bladder cancer predicts the preventive effect of androgen deprivation therapy on tumor recurrence

// Koji Izumi 1,2,* , Yusuke Ito 1,* , Hiroshi Miyamoto 3 , Yasuhide Miyoshi 4 , Junichi Ota 2 , Masatoshi Moriyama 2 , Tetsuo Murai 5 , Hiroyuki Hayashi 6 , Yoshiaki Inayama 7 , Kenichi Ohashi 8 , Masahiro Yao 1 and Hiroji Uemura 4 1 Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan 2 Department of Urology, Yokohama Municipal Citizen’s Hospital, Yokohama, Japan 3 Departments of Pathology and Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA 4 Department of Urology, Yokohama City University Medical Center, Yokohama, Japan 5 Department of Urology, International Goodwill Hospital, Yokohama, Japan 6 Department of Pathology, Yokohama Municipal Citizen’s Hospital, Yokohama, Japan 7 Department of Pathology, Yokohama City University Medical Center, Yokohama, Japan 8 Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan * These authors have contributed equally to this work Correspondence to: Koji Izumi, email: // Keywords : bladder cancer, recurrence, androgen receptor, androgen deprivation therapy Received : November 04, 2015 Accepted : January 29, 2016 Published : February 12, 2016 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.