title: Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer.
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.
  
  
  METHODS
  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.
authors.affiliation: St Josef Medical Centre, Department of Urology of Regensburg University, Regensburg, Germany. wolfgang.otto@klinik.uni-regensburg.de
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Otto
authors.forename: Peter C
authors.initials: PC
authors.lastname: Rubenwolf
authors.forename: Maximilian
authors.initials: M
authors.lastname: Burger
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Fritsche
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rößler
authors.forename: Matthias
authors.initials: M
authors.lastname: May
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Hofstädter
authors.forename: Wolf F
authors.initials: WF
authors.lastname: Wieland
authors.forename: Stefan
authors.initials: S
authors.lastname: Denzinger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051400:Aquaporin 3 / Q000096:biosynthesis*; D001500:BCG Vaccine / Q000008:administration & dosage / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: D001500:BCG Vaccine; D014408:Biomarkers, Tumor; D051400:Aquaporin 3