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

Koji Izumi,Tetsuo Murai,Masahiro Yao,Yusuke Ito,Hiroyuki Hayashi,Masatoshi Moriyama,Yoshiaki Inayama,Yasuhide Miyoshi,Kenichi Ohashi,Hiroji Uemura,Junichi Ota,Hiroshi Miyamoto

doi:10.18632/oncotarget.7358

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.

Highlights

Men have 3-4 times higher incidence of bladder cancer (BC) than women [1]
80% of patients are present with non-muscle-invasive BC (NMIBC) at the initial diagnosis, 36-51% of them recur despite of currently available adjuvant instillation therapy, such as intravesical instillation of an anthracycline or www.impactjournals.com/oncotarget bacillus Calmette-Guérin (BCG), and approximately 10% of them eventually progressed to muscle invasion [2]
The purpose of this study is to investigate the associations between androgen receptor (AR)/ERα/ERβ expression in surgical specimens and BC recurrence in patients treated with androgen deprivation therapy (ADT)

Summary

Introduction

80% of patients are present with non-muscle-invasive BC (NMIBC) at the initial diagnosis, 36-51% of them recur despite of currently available adjuvant instillation therapy, such as intravesical instillation of an anthracycline or www.impactjournals.com/oncotarget bacillus Calmette-Guérin (BCG), and approximately 10% of them eventually progressed to muscle invasion [2]. New treatment is urgently needed to prevent both recurrence and progression of BC. Prognostic significance of AR expression in BC recurrence is still controversial [7,8,9,10,11]. There is no significant gender-specific difference in the expression levels of AR [7], suggesting that circulating serum androgens may be critical for AR-stimulated BC development

Objectives

Results

Discussion

Conclusion