title: Epithelial-mesenchymal transformation markers E-cadherin and survivin predict progression of stage pTa urothelial bladder carcinoma.
abstract: OBJECTIVE
  To determine whether the immunohistochemical markers survivin and E-cadherin can predict progress at initially diagnosed Ta bladder cancer.
  
  
  METHODS
  We retrospectively searched for every initially diagnosed pTa urothelial bladder carcinoma having been treated at our single-center hospital in Germany from January 1992 up to December 2004. Follow-up was recorded up to June 2010, with recurrence or progress being the endpoints. Immunohistochemical staining and analysis of survivin and E-cadherin of the TURB specimens were performed. Outcome dependency of progression and no progression with immunohistochemical staining was analyzed using uni- and multivariate regression analysis, Kaplan-Meier analysis and uni- and multivariate Cox regression analysis.
  
  
  RESULTS
  Overall, 233 patients were included. Forty-two percent of those were tumor free in their follow-up TURBs, 46 % had at least one pTa recurrence and 12 % even showed progress to at least pT1 bladder cancer. Aberrant staining of E-cadherin was found within 71 % of patients with progression in contrast to only 40 % in cases without progression (p = 0.004). Of all progressed patients, 92 % showed overexpression of survivin in their initial pTa specimen compared to 61 % without progression (p = 0.001). Kaplan-Meier analysis revealed aberrant E-cadherin staining to be associated with worse progression-free survival (PFS) (p = 0.005) as well as overexpression of survivin (p = 0.003). In multivariate Cox regression analysis, strong E-cadherin staining was an independent prognosticator for better PFS (p = 0.033) and multifocality (p = 0.046) and tumor size over 3 cm (p = 0.042) were prognosticators for worse PFS.
  
  
  CONCLUSIONS
  Adding the immunohistochemical markers survivin and E-cadherin could help to identify patients at risk of developing a progressive disease in initial stage pTa bladder cancer.
authors.affiliation: Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Landshuter Str. 65, 93053, Regensburg, Germany. Johannes.Breyer@ukr.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Breyer
authors.affiliation: Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Landshuter Str. 65, 93053, Regensburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gierth
authors.affiliation: Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Landshuter Str. 65, 93053, Regensburg, Germany.
authors.forename: Sanzhar
authors.initials: S
authors.lastname: Shalekenov
authors.affiliation: Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Landshuter Str. 65, 93053, Regensburg, Germany.|Department of Urology, University of Hamburg, Hamburg, Germany.
authors.forename: Atiqullah
authors.initials: A
authors.lastname: Aziz
authors.affiliation: Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Landshuter Str. 65, 93053, Regensburg, Germany.
authors.forename: Julius
authors.initials: J
authors.lastname: Schäfer
authors.affiliation: Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Landshuter Str. 65, 93053, Regensburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Burger
authors.affiliation: Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Landshuter Str. 65, 93053, Regensburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Denzinger
authors.affiliation: Institute of Pathology, University of Regensburg, Regensburg, Germany.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Hofstädter
authors.affiliation: Institute of Pathology, University of Regensburg, Regensburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Giedl
authors.affiliation: Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Landshuter Str. 65, 93053, Regensburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Otto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D015820:Cadherins / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000737:chemistry* / Q000473:pathology*; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D000077022:Survivin; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000473:pathology*
chemical_list: D015703:Antigens, CD; C107489:BIRC5 protein, human; C513384:CDH1 protein, human; D015820:Cadherins; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin
keywords: E-cadherin; EMT; Immunohistochemistry; Non-muscle-invasive bladder cancer; Stage pTa bladder cancer; Survivin