title: Low levels of WWOX protein immunoexpression correlate with tumour grade and a less favourable outcome in patients with urinary bladder tumours.
abstract: OBJECTIVE
  To correlate the immunohistochemical detection of WWOX with histological measures and disease progression within the whole spectrum of urothelial bladder neoplasms.
  
  
  RESULTS
  One hundred and one patients with primary bladder tumours were retrospectively analysed. Immunohistochemically, a polyclonal antibody was utilized and the level of WWOX protein expression was analysed by using a combined score system based on intensity of the reaction and percentage of immunoreactive tumour cells. WWOX protein expression was consistently expressed in non-neoplastic urothelium, whereas a progressive loss of immunoreactivity was observed as tumour grade and stage increased (P < 0.05). Principal component analysis showed that reduced WWOX immunoexpression was significantly associated with high histological grades (P = 0.001), advanced stage (P = 0.002), tumour size (P = 0.04) and cancer progression (P = 0.028). Invasive urothelial carcinomas of the bladder with squamous metaplasia presented the lowest levels of WWOX protein. Kaplan-Meier analyses demonstrated a significant correlation between loss of WWOX expression and a shorter progression-free survival (P = 0.042), whereas the prediction of overall survival achieved borderline significance (P = 0.053).
  
  
  CONCLUSIONS
  Loss of WWOX immunoexpression strongly correlates with classical clinicopathological factors and appears to be a potential predictive marker of progressive disease.
authors.affiliation: Department of Pathology, School of Medicine, University of Valencia, Valencia, Spain. david.ramos@uv.es
authors.forename: D
authors.initials: D
authors.lastname: Ramos
authors.forename: M
authors.initials: M
authors.lastname: Abba
authors.forename: J A
authors.initials: JA
authors.lastname: López-Guerrero
authors.forename: J
authors.initials: J
authors.lastname: Rubio
authors.forename: E
authors.initials: E
authors.lastname: Solsona
authors.forename: S
authors.initials: S
authors.lastname: Almenar
authors.forename: A
authors.initials: A
authors.lastname: Llombart-Bosch
authors.forename: C M
authors.initials: CM
authors.lastname: Aldaz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D002452:Cell Count; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000378:metabolism*; D012189:Retrospective Studies; D013030:Spain / Q000453:epidemiology; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D019459:Urothelium / Q000378:metabolism / Q000473:pathology; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human