High Androgen Receptor mRNA Expression Is Independently Associated with Prolonged Cancer-Specific and Recurrence-Free Survival in Stage T1 Bladder Cancer

Abstract

INTRODUCTION: High-risk non–muscle-invasive bladder cancer (NMIBC) remains challenging given the high probability of progression. Given that the androgen receptor (AR) has been discussed as a possible factor in the development and progression of bladder cancer, we investigated the predictive value of AR in stage pT1 NMIBC. MATERIALS AND METHODS: We retrospectively analyzed the clinical data and AR mRNA expression in 296 patients with stage pT1 NMIBC who underwent a transurethral resection of the bladder. The mRNA expression of the AR transcript variants 1 (AR1) and 2 (AR2) was measured by reverse transcription quantitative real-time polymerase chain reaction. AR expression was also correlated to KRT5 and KRT20 mRNA expression. RESULTS: Kaplan-Meier analysis indicated that high AR1 mRNA expression ≥35.47 is associated with statistically significant better recurrence-free survival (RFS) (P = .0007), progression-free survival (PFS) (P = .0420), and cancer-specific survival (CSS) (P = .0050). Multivariate Cox regression analysis revealed that high AR1 mRNA expression is an independent prognostic marker for RFS (P = .0029) and CSS (P = .0119). Spearman rank correlation revealed a significant positive association between mRNA expression of AR1 and KRT5 (rs: 0.3171, P < .0001) as well as a negative association with multifocal tumors (rs: 0.1478, P < .0109). No association was noted between AR1 expression and tumor grade, concomitant CIS, gender, tumor size, and KRT20 in patients with stage T1 NMIBC. CONCLUSIONS: AR mRNA expression can predict RFS and CSS in patients with stage T1 NMIBC. Further studies are necessary to refine the relevance of AR mRNA expression compared with immunohistochemically detectable AR expression.

mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants

“…As demonstrated previously in NMIBC, the assessment of cytokeratin (CK) 5 and CK20 protein expression by immunohistochemistry correlates well with KRT5 and KRT20 mRNA expression but lacks prognostic value [ 21 ], which is in line with previous breast cancer studies investigating MKI67 (marker of proliferation Ki-67) , ER (estrogen receptor) , ERBB2 (Erb-B2 Receptor Tyrosine Kinase 2) , and PR (progesterone receptor) mRNA and protein expression [ 37 ]. Therefore, RT-qPCR has been considered as a possible alternative for immunohistochemistry, as it is objective and not affected by interobserver variability [ 37 , 38 , 39 , 40 ]. Furthermore, simple gene expression assays in a ready-to-use format are quite simple to establish and to perform on small devices (e.g., Cepheid approaches) compared to immunohistochemistry on expansive autostainers.…”

Androgen Receptor mRNA Expression in Urothelial Carcinoma of the Bladder: A Retrospective Analysis of Two Independent Cohorts

“…The conflicting results of the previously cited studies might in part be attributed to immunohistochemistry as the main method to determine AR expression, since immunohistochemistry is associated with high inter-observer variability depending on the antibodies used and different cut-off values [16]. In a recent study, we were able to identify improved survival for patients with stage T1 bladder cancer and high AR mRNA expression measured with quantitative real-time polymerase chain reaction [17].…”

Analysis of CXCL9, PD1 and PD-L1 mRNA in Stage T1 Non-Muscle Invasive Bladder Cancer and Their Association with Prognosis

“…Tumor specimens were assessed by qRT-PCR as previously described [ 43 ]. In short, RNA was extracted from a single 10 μm curl of FFPE tissue and processed according to a commercially available bead-based extraction method (Xtract kit; Stratifyer Molecular Pathology GmbH, Cologne, Germany).…”