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Open Access Research article

Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer

Wolfgang Otto1*, Peter C Rubenwolf2, Maximilian Burger3, Hans-Martin Fritsche1, Wolfgang Rößler1, Matthias May4, Arndt Hartmann5, Ferdinand Hofstädter6, Wolf F Wieland1 and Stefan Denzinger1

Author affiliations

1 St. Josef Medical Centre, Department of Urology of Regensburg University, Regensburg, Germany

2 Mainz University Medical Center, Johannes Gutenberg University, Department of Urology, Mainz, Germany

3 Department of Urology, University of Würzburg, Würzburg, Germany

4 Department of Urology, Klinikum St. Elisabeth, Straubing, Germany

5 Institute of Pathology, University of Erlangen, Erlangen, Germany

6 Institute of Pathology, University of Regensburg, Regensburg, Germany

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Citation and License

BMC Cancer 2012, 12:459  doi:10.1186/1471-2407-12-459

Published: 8 October 2012

Abstract

Background

Treatment of patients with stage pT1 urothelial bladder cancer (UBC) continues to be a challenge due to its unpredictable clinical course. Reliable molecular markers that help to determine appropriate individual treatment are still lacking. Loss of aquaporin (AQP) 3 protein expression has previously been shown in muscle-invasive UBC. The aim of the present study was to investigate the prognostic value of AQP3 protein expression with regard to the prognosis of stage pT1 UBC.

Method

AQP 3 protein expression was investigated by immunohistochemistry in specimens of 87 stage T1 UBC patients, who were diagnosed by transurethral resection of the bladder (TURB) and subsequent second resection at a high-volume urological centre between 2002 and 2009. Patients underwent adjuvant instillation therapy with Bacillus Calmette-Guérin (BCG). Loss of AQP3 protein expression was defined as complete absence of the protein within the whole tumour. Expression status was correlated retrospectively with clinicopathological and follow-up data (median: 31 months). Multivariate Cox regression analysis was used to assess the value of AQP3 tumour expression with regard to recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS). RFS, PFS and CSS were calculated by Kaplan-Meier analysis and Log rank test.

Results

59% of patients were shown to exhibit AQP3-positive tumours, whereas 41% of tumours did not express the marker. Loss of AQP3 protein expression was associated with a statistically significantly worse PFS (20% vs. 72%, p=0.020). This finding was confirmed by multivariate Cox regression analysis (HR 7.58, CI 1.29 – 44.68; p=0.025).

Conclusions

Loss of AQP3 protein expression in pT1 UBC appears to play a key role in disease progression and is associated with worse PFS. Considering its potential prognostic value, assessment of AQP3 protein expression could be used to help stratify the behavior of patients with pT1 UBC.

Keywords:
Urothelial bladder carcinoma; Stage pT1; Aquaporin 3 protein; Immunohistochemistry; Progression