Wolfgang Otto1, Johannes Breyer2, Sonja Herdegen1, Fabian Eder3, Simone Bertz4, Matthias May5, Roman Mayr1, Eva M Lausenmeyer1, Stefan Denzinger1, Bas W G van Rhijn1,6, Maximilian Burger1, Arndt Hartmann4. 1. Department of Urology, University of Regensburg, Landshuterstr. 65, 93053, Regensburg, Germany. 2. Department of Urology, University of Regensburg, Landshuterstr. 65, 93053, Regensburg, Germany. Johannes.breyer@ukr.de. 3. Institute of Pathology, University of Regensburg, Regensburg, Germany. 4. Institute of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany. 5. Department of Urology, Hospital St. Elisabeth, Straubing, Germany. 6. Department of Surgical Oncology (Urology), Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Abstract
PURPOSE: 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.
PURPOSE: Stage pT1urothelial 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 UBCpatients 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: Simone Bertz; Stefan Denzinger; Wolfgang Otto; Wolf F Wieland; Robert Stoehr; Ferdinand Hofstaedter; Arndt Hartmann Journal: Histopathology Date: 2011-10 Impact factor: 5.087
Authors: Wolfgang Otto; Stefan Denzinger; Hans-Martin Fritsche; Maximilian Burger; Wolf F Wieland; Ferdinand Hofstädter; Arndt Hartmann; Simone Bertz Journal: BJU Int Date: 2010-08-12 Impact factor: 5.588
Authors: Stefan Denzinger; Maximilian Burger; Hans-Martin Fritsche; Simone Bertz; Ferdinand Hofstädter; Wolf F Wieland; Arndt Hartmann; Wolfgang Otto Journal: Scand J Urol Nephrol Date: 2009
Authors: Edward C Ottley; Robert Pell; Benedict Brazier; Julianne Hollidge; Christiana Kartsonaki; Lisa Browning; Eric O'Neill; Anne E Kiltie Journal: J Pathol Clin Res Date: 2020-05-06