nach oben

Erschienen in:

01.12.2015 | Original Article

Loss of AQP3 protein expression is associated with worse progression-free and cancer-specific survival in patients with muscle-invasive bladder cancer

verfasst von: Peter Rubenwolf, Christian Thomas, Stefan Denzinger, Arndt Hartmann, Maximilian Burger, Nikolaos T. Georgopoulos, Wolfgang Otto

Erschienen in: World Journal of Urology | Ausgabe 12/2015

Einloggen, um Zugang zu erhalten

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.

Green DA, Rink M, Xylinas E et al (2013) Urothelial carcinoma of the bladder and the upper tract: disparate twins. J Urol 189(4):1214–1221CrossRefPubMed

Rubenwolf PC, Georgopoulos NT, Clements LA et al (2009) Expression and localisation of aquaporin water channels in human urothelium in situ and in vitro. Eur Urol 56(6):1013–1023CrossRefPubMed

Rubenwolf PC, Georgopoulos NT, Kirkwood LA, Baker SC, Southgate J (2012) Aquaporin expression contributes to human transurothelial permeability in vitro and is modulated by NaCl. PLoS ONE 7(9):e45339PubMedCentralCrossRefPubMed

Saadoun S, Papadopoulos MC, Hara-Chikuma M, Verkman AS (2005) Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption. Nature 434(7034):786–792CrossRefPubMed

Rubenwolf PC, Otto W, Denzinger S, Hofstadter F, Wieland W, Georgopoulos NT (2014) Expression of aquaporin water channels in human urothelial carcinoma: correlation of AQP3 expression with tumour grade and stage. World J Urol 32(4):991–997CrossRefPubMed

Otto W, Rubenwolf PC, Burger M et al (2012) Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer. BMC Cancer 12:459PubMedCentralCrossRefPubMed

Cheng L, Davison DD, Adams J et al (2014) Biomarkers in bladder cancer: translational and clinical implications. Crit Rev Oncol Hematol 89(1):73–111CrossRefPubMed

Frantzi M, Makridakis M, Vlahou A (2012) Biomarkers for bladder cancer aggressiveness. Curr Opin Urol 22(5):390–396CrossRefPubMed

Hautmann RE, de Petriconi RC, Pfeiffer C, Volkmer BG (2012) Radical cystectomy for urothelial carcinoma of the bladder without neoadjuvant or adjuvant therapy: long-term results in 1100 patients. Eur Urol 61(5):1039–1047CrossRefPubMed

10.

Burger M, Mulders P, Witjes W (2012) Use of neoadjuvant chemotherapy for muscle-invasive bladder cancer is low among major European centres: results of a feasibility questionnaire. Eur Urol 61(5):1070–1071CrossRefPubMed

11.

Kusayama M, Wada K, Nagata M et al (2011) Critical role of aquaporin 3 on growth of human esophageal and oral squamous cell carcinoma. Cancer Sci 102(6):1128–1136CrossRefPubMed

12.

Huang Y, Zhu Z, Sun M et al (2010) Critical role of aquaporin-3 in the human epidermal growth factor-induced migration and proliferation in the human gastric adenocarcinoma cells. Cancer Biol Ther 9(12):1000–1007CrossRefPubMed

13.

Jablonski EM, Mattocks MA, Sokolov E et al (2007) Decreased aquaporin expression leads to increased resistance to apoptosis in hepatocellular carcinoma. Cancer Lett 250(1):36–46PubMedCentralCrossRefPubMed

Titel: Loss of AQP3 protein expression is associated with worse progression-free and cancer-specific survival in patients with muscle-invasive bladder cancer
verfasst von: Peter Rubenwolf
Christian Thomas
Stefan Denzinger
Arndt Hartmann
Maximilian Burger
Nikolaos T. Georgopoulos
Wolfgang Otto
Publikationsdatum: 01.12.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: World Journal of Urology / Ausgabe 12/2015
Print ISSN: 0724-4983
Elektronische ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-015-1574-8

Update Urologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Loss of AQP3 protein expression is associated with worse progression-free and cancer-specific survival in patients with muscle-invasive bladder cancer