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.

Expression and clinical significance of androgen receptor in bladder cancer: A meta-analysis

“…Finally, data were available from five studies on AR expression and bladder cancer susceptibility (568 tumor cases vs. 523 normal controls), six studies on AR expression and tumor grade (387 low grade vs. 663 high grade cases), nine studies on AR expression and tumor stage (582 non-invasive vs. 712 invasive cases), five studies on AR expression and RFS (414 cases) and four studies on AR expression and PFS (319 cases). The essential information of the included studies was listed in Table I ( [8][9][10][11][19][20][21][22][23][24][25][26].…”

“…Recently, the controversial relationship between AR expression and bladder cancer prognosis has been reported. Studies by Nam et al (23) and Izumi et al (26) indicated that AR-positive patients had a significantly lower risk of tumor recurrence compared with those with AR-negative tumors. Contrastingly, Mir et al (11) demonstrated that loss of AR expression was not associated with clinical outcome, including RFS.…”

The impact of advanced proteomics in the search for markers and therapeutic targets of bladder cancer

“…A wide variety of gene expression differences related to cell cycle regulators, proliferation antigens, cell adhesion molecules, and signaling proteins have been investigated for a better assessment of superficial BC prognosis. 10,90,91 Based on the urinary proteome database, Feng et al 92 used bioinformatics to construct a cancer-associated PPI network comprising 16 high-abundance urinary proteins. Following an analysis, it was shown that platelet-derived growth factor receptor beta (PDGFRB) was significantly increased in relapsed patients (n = 68) than in relapse-free patients (n = 117, p < 0.001), and it was significantly correlated with the increased risk of 3-year recurrence in superficial BC.…”

Role of 5‑Aza‑CdR in mitomycin‑C chemosensitivity of T24 bladder cancer cells

“…Muscle-invasive bladder cancer constitutes ~30% of newly diagnosed cases of bladder cancer (2). Approximately 10% of non-invasive bladder cancer cases eventually progress to invasive cancer following the transurethral resection of the bladder tumor (3). Compared with non-invasive bladder cancer, patients with invasive disease have a poor prognosis, with a 5-year survival rate of 50% (4).…”