Receptor Activator of NF Kappa B (RANK) Expression Indicates Favorable Prognosis in Patients with Muscle-invasive Bladder Cancer.

Receptor activator of NF kappa B (RANK) and its ligand have an essential role in T-cell regulation and the development of bone metastases. The role of RANK expression in muscle-invasive bladder cancer (MIBC) is unknown.

To assess the relevance of RANK expression in patients with MIBC.

Expression of RANK was assessed via immunohistochemistry of benign urothelium, MIBC tissue, and lymph node metastases from 153 patients undergoing radical cystectomy. Expression data from The Cancer Genome Atlas (TCGA) cohort were analyzed for potential associations with molecular subtypes and outcome.

RANK expression was correlated with clinical and pathological parameters and to individual data for the clinical course of MIBC.

Expression of RANK was significantly higher in both primary tumors (p = 0.02) and lymph node metastases (p = 0.01) compared to normal urothelium. In tumor tissue, RANK expression was significantly lower in patients with locally advanced disease and lymph node involvement compared to those with organ-confined disease (p = 0.0009) and node-negative MIBC (p = 0.0002). In univariable and multivariable analyses, high expression of RANK was associated with a longer time to recurrence (p = 0.0005 and 0.01) and better cancer-specific (p = 0.0004 and 0.007) and overall survival (p = 0.002 and 0.04). High expression of RANK was associated with better outcome for patients with luminal infiltrated tumors in the TCGA cohort.

RANK expression is increased in bladder cancer tissue compared to benign urothelium, with higher expression in organ-defined compared to locally advanced disease. High RANK expression indicates a favorable prognosis in MIBC. The prognostic role differs in tumors of different molecular subtypes.

Expression of a protein involved in bone turnover regulation (RANK) is higher in bladder cancer tissue than in benign bladder tissue. However, high levels of RANK on tumor cells indicate favorable prognosis for patients with bladder cancer that invades the muscle layer of the bladder.

European urology focus. 2021 May 04 [Epub ahead of print]

Moritz Maas, Steffen Rausch, Teresa Guttenberg, Roland Seiler, Jörg Hennenlotter, Htoo Zarni Oo, Ladan Fazli, Ursula Kühs, Georgios Gakis, Arnulf Stenzl, Christian Schwentner, Peter C Black, Tilman Todenhöfer

Department of Urology, University Hospital, Tübingen, Germany., Cardiovascular Center, Oberallgäu-Kempten, Kempten, Germany., Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Department of Urology, University Hospital, Bern, Switzerland., Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada., Department of Urology, University Hospital, Würzburg, Germany., Department of Urology, Diakonie Klinik, Stuttgart, Germany., Department of Urology, University Hospital, Tübingen, Germany; Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Clinical Trials Unit, Studienpraxis Urologie, Nürtingen, Germany. Electronic address: .