title: WHO 1973 grade 3 and infiltrative growth pattern proved, aberrant E-cadherin expression tends to be of predictive value for progression in a series of stage T1 high-grade bladder cancer after organ-sparing approach.
abstract: OBJECTIVE
  Stage pT1 urothelial bladder cancer (UBC) is characterized as a challenging subentity of urothelial carcinoma with an unforeseeable clinical course. In addition to more or less established clinical and histopathological features, we evaluated the role of epithelial-mesenchymal transition (EMT) marker E-cadherin, shown to be of prognostic value in muscle-invasive disease, regarding the prognosis of stage pT1 high-grade (hg) UBC.
  
  
  METHODS
  Tissue of 226 stage pT1 hg UBC patients from transurethral resection could be immunostained for E-cadherin. Kaplan-Meier analysis and univariate and multivariate Cox regression analyses regarding progression-free (PFS) and cancer-specific survival (CSS) were performed.
  
  
  RESULTS
  Aberrant expression of E-cadherin was recognized in 74% of patients. Kaplan-Meier analysis showed that aberrant E-cadherin expression was associated with worse 10-year PFS (62 vs. 90%, p = 0.045). In univariate analysis, aberrant E-cadherin staining, associated carcinoma in situ, grading 3 after WHO classification 1973 and infiltrative growth pattern at the invasion front were the statistically significant predictive factors for worse PFS, only infiltrative growth pattern for CSS. With regard to progression, grading 3 after WHO classification of 1973 (HR 6.49; CI 1.54-27.28, p = 0.011) and infiltrative tumor invasion pattern (HR 2.06; CI 1.10-3.86, p = 0.024) revealed as independent factors for PFS, and there was a trend also for E-cadherin expression (HR 0.45; CI 0.19-1.06; p = 0.068). Regarding CSS, infiltrative tumor growth pattern (HR 3.79; CI 1.67-8.60, p = 0.001) was the only statistically significantly independent predictive factor in multivariate Cox regression analysis.
  
  
  CONCLUSIONS
  Beside invasion growth pattern and WHO grading 1973 that achieved to be independent prognostic factors, there was a trend for the parameter E-cadherin expression to be of predictive value for PFS in stage pT1 hg urothelial bladder carcinoma after organ-sparing approach. Further studies on genetic level are warranted to define the distinct role of EMT in early-invasive UBC.
authors.affiliation: Department of Urology, University of Regensburg, Landshuterstr. 65, 93053, Regensburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Otto
authors.affiliation: Department of Urology, University of Regensburg, Landshuterstr. 65, 93053, Regensburg, Germany. Johannes.breyer@ukr.de.
authors.forename: Johannes
authors.identifier: http://orcid.org/0000-0003-0674-4150
authors.initials: J
authors.lastname: Breyer
authors.affiliation: Department of Urology, University of Regensburg, Landshuterstr. 65, 93053, Regensburg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Herdegen
authors.affiliation: Institute of Pathology, University of Regensburg, Regensburg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Eder
authors.affiliation: Institute of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Bertz
authors.affiliation: Department of Urology, Hospital St. Elisabeth, Straubing, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: May
authors.affiliation: Department of Urology, University of Regensburg, Landshuterstr. 65, 93053, Regensburg, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Mayr
authors.affiliation: Department of Urology, University of Regensburg, Landshuterstr. 65, 93053, Regensburg, Germany.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Lausenmeyer
authors.affiliation: Department of Urology, University of Regensburg, Landshuterstr. 65, 93053, Regensburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Denzinger
authors.affiliation: Department of Urology, University of Regensburg, Landshuterstr. 65, 93053, Regensburg, Germany.|Department of Surgical Oncology (Urology), Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Bas W G
authors.initials: BW
authors.lastname: van Rhijn
authors.affiliation: Department of Urology, University of Regensburg, Landshuterstr. 65, 93053, Regensburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Burger
authors.affiliation: Institute of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D015820:Cadherins / Q000032:analysis*; D002278:Carcinoma in Situ / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D002295:Carcinoma, Transitional Cell / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D059351:Organ Sparing Treatments; D011237:Predictive Value of Tests; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins
keywords: E-cadherin; Epithelial–mesenchymal transition; Immunohistochemistry; Stage pT1 bladder cancer; WHO grading classifications