Peter Rubenwolf1, Christian Thomas2, Stefan Denzinger3, Arndt Hartmann4, Maximilian Burger3, Nikolaos T Georgopoulos5, Wolfgang Otto3. 1. Department of Urology, Mainz University Medical Center, Langenbeckstrasse 1, 55131, Mainz, Germany. peterrubenwolf@gmx.de. 2. Department of Urology, Mainz University Medical Center, Langenbeckstrasse 1, 55131, Mainz, Germany. 3. Department of Urology, University of Regensburg, Regensburg, Germany. 4. Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuernberg, Erlangen, Germany. 5. Department of Biology, School of Applied Sciences, University of Huddersfield, Huddersfield, UK.
Abstract
PURPOSE: Urothelial carcinoma has recently been shown to express several aquaporins (AQP), with AQP3 being of particular interest as its expression is reduced or lost in tumours of higher grade and stage. Loss of AQP3 expression was associated with worse progression-free survival (PFS) in patients with pT1 bladder cancer. The objective of this study was to investigate the prognostic value of AQP3 expression in patients with muscle-invasive bladder carcinoma (MIBC). METHODS: Retrospective single-centre analysis of the oncological outcome of patients following radical cystectomy (Cx) due to MIBC. Immunohistochemistry was used to assess AQP3 protein expression in 100 Cx specimens. Expression levels of AQP3 were related to clinicopathological variables. The impact of biomarker expression on progression-free, cancer-specific and overall survival was determined by multivariate Cox regression analysis (MVA). RESULTS: High expression of AQP3 by the tumour was associated with a statistically significantly improved PFS (75 vs. 19 %, p = 0.043) and CSS (75 vs. 18 %, p = 0.030) and, alongside lymph node involvement, was an independent predictor of PFS (HR 2.871, CI 1.066-7.733, p = 0.037), CSS (HR 3.325, CI 1.204-8.774, p = 0.019) and OS (HR 2.001, CI 1.014-3.947) in MVA. CONCLUSIONS: Although the results of the study would be strengthened by a larger, more appropriately powered, prospective, multi-institutional study, our findings strongly suggest that AQP3 expression status may represent an independent predictor of PFS and CSS in MIBC and may help select patients in need for (neo-)adjuvant chemotherapy.
PURPOSE:Urothelial carcinoma has recently been shown to express several aquaporins (AQP), with AQP3 being of particular interest as its expression is reduced or lost in tumours of higher grade and stage. Loss of AQP3 expression was associated with worse progression-free survival (PFS) in patients with pT1 bladder cancer. The objective of this study was to investigate the prognostic value of AQP3 expression in patients with muscle-invasive bladder carcinoma (MIBC). METHODS: Retrospective single-centre analysis of the oncological outcome of patients following radical cystectomy (Cx) due to MIBC. Immunohistochemistry was used to assess AQP3 protein expression in 100 Cx specimens. Expression levels of AQP3 were related to clinicopathological variables. The impact of biomarker expression on progression-free, cancer-specific and overall survival was determined by multivariate Cox regression analysis (MVA). RESULTS: High expression of AQP3 by the tumour was associated with a statistically significantly improved PFS (75 vs. 19 %, p = 0.043) and CSS (75 vs. 18 %, p = 0.030) and, alongside lymph node involvement, was an independent predictor of PFS (HR 2.871, CI 1.066-7.733, p = 0.037), CSS (HR 3.325, CI 1.204-8.774, p = 0.019) and OS (HR 2.001, CI 1.014-3.947) in MVA. CONCLUSIONS: Although the results of the study would be strengthened by a larger, more appropriately powered, prospective, multi-institutional study, our findings strongly suggest that AQP3 expression status may represent an independent predictor of PFS and CSS in MIBC and may help select patients in need for (neo-)adjuvant chemotherapy.
Authors: David A Green; Michael Rink; Evanguelos Xylinas; Surena F Matin; Arnulf Stenzl; Morgan Roupret; Pierre I Karakiewicz; Douglas S Scherr; Shahrokh F Shariat Journal: J Urol Date: 2012-09-27 Impact factor: 7.450
Authors: Peter C Rubenwolf; Nikolaos T Georgopoulos; Lisa A Clements; Sally Feather; Philip Holland; David F M Thomas; Jennifer Southgate Journal: Eur Urol Date: 2008-08-13 Impact factor: 20.096
Authors: Peter C Rubenwolf; Nikolaos T Georgopoulos; Lisa A Kirkwood; Simon C Baker; Jennifer Southgate Journal: PLoS One Date: 2012-09-24 Impact factor: 3.240