Loss of AQP3 protein expression is associated with worse progression-free and cancer-specific survival in patients with muscle-invasive bladder cancer.
OBJECTIVE
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.
Department of Urology, Mainz University Medical Center, Langenbeckstrasse 1, 55131, Mainz, Germany. peterrubenwolf@gmx.de.
Peter
P
Rubenwolf
Department of Urology, Mainz University Medical Center, Langenbeckstrasse 1, 55131, Mainz, Germany.
Christian
C
Thomas
Department of Urology, University of Regensburg, Regensburg, Germany.
Stefan
S
Denzinger
Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuernberg, Erlangen, Germany.
Arndt
A
Hartmann
Department of Urology, University of Regensburg, Regensburg, Germany.
Maximilian
M
Burger
Department of Biology, School of Applied Sciences, University of Huddersfield, Huddersfield, UK.
Nikolaos T
NT
Georgopoulos
Department of Urology, University of Regensburg, Regensburg, Germany.
Wolfgang
W
Otto
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051400:Aquaporin 3 / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D019459:Urothelium
D051400:Aquaporin 3
Aquaporin 3 (AQP3); Biomarker; Cancer-specific survival; Muscle-invasive bladder cancer; Muscle-invasive urothelial carcinoma; Oncological outcome; Prognosis; Prognostic value