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Increased Proliferation as Independent Predictor of Disease Recurrence in Initial Stage pTa Urothelial Bladder Cancer

OBJECTIVES: To investigate the predictive impact of the proliferation biomarker Ki-67 on the clinical course of patients with initial stage pTa urothelial carcinoma of the bladder (UCB). METHODS: We retrospectively analyzed all patients treated by transurethral resection of bladder tumors (TUR-B) fo...

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Autores principales: Breyer, Johannes, Shalekenov, Sanzhar, Aziz, Atiqullah, van Rhijn, Bastiaan W.G., Bründl, Johannes, Lausenmeyer, Eva, Schäfer, Julius, Denzinger, Stefan, Giedl, Christian, Burger, Maximilian, Hartmann, Arndt, Evert, Matthias, Otto, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545917/
https://www.ncbi.nlm.nih.gov/pubmed/28824945
http://dx.doi.org/10.3233/BLC-170103
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author Breyer, Johannes
Shalekenov, Sanzhar
Aziz, Atiqullah
van Rhijn, Bastiaan W.G.
Bründl, Johannes
Lausenmeyer, Eva
Schäfer, Julius
Denzinger, Stefan
Giedl, Christian
Burger, Maximilian
Hartmann, Arndt
Evert, Matthias
Otto, Wolfgang
author_facet Breyer, Johannes
Shalekenov, Sanzhar
Aziz, Atiqullah
van Rhijn, Bastiaan W.G.
Bründl, Johannes
Lausenmeyer, Eva
Schäfer, Julius
Denzinger, Stefan
Giedl, Christian
Burger, Maximilian
Hartmann, Arndt
Evert, Matthias
Otto, Wolfgang
author_sort Breyer, Johannes
collection PubMed
description OBJECTIVES: To investigate the predictive impact of the proliferation biomarker Ki-67 on the clinical course of patients with initial stage pTa urothelial carcinoma of the bladder (UCB). METHODS: We retrospectively analyzed all patients treated by transurethral resection of bladder tumors (TUR-B) for UCB between 1992–2004 in a single-center. Disease recurrence (≥pTa UCB) and absent tumor in histopathology, assessed by TUR-B with a non-malignant result for endoscopic suspect bladder lesion displayed endpoints. Immunohistochemical (IHC) analysis of formalin-fixed and paraffin-embedded tissue blocks was performed with an immunostainer using a primary antibody for Ki-67. Semiquantitative evaluation of Ki-67 was performed by three reviewers. Increased proliferation was defined with a cut-off value of ≥50%. Uni- and multivariable binary regression analyses were applied to address prediction of disease recurrence. RESULTS: 215 patients (84% male, median age 69 years at first diagnosis) were evaluable and included to the study. 89 patients stayed disease-free (41%), 126 patients showed recurrence (59%). Recurrence rates of patients with Ki-67 expression <10%, 10–24%, 25–49% and ≥50% were 14.8% vs. 30.8% vs. 63.9% and 80.7%, respectively (p < 0.001). In Kaplan-Meier analysis patients with increased proliferation ≥50% showed a statistically significant worse 10-year recurrence-free survival (19% vs. 57%, p < 0.001). Multivariable regression analysis revealed instillation treatment (p = 0.001) and high proliferation of Ki-67 (p < 0.001) to be independent predictors of recurrence in stage pTa UCB. CONCLUSIONS: High proliferation with Ki-67 expression ≥50% was strongly associated with worse recurrence-free survival in patients with initial stage pTa UCB. Stage pTa UCB patients with increased Ki-67 expression should undergo a strictly follow-up regime comparable to stage pT1 bladder carcinoma, while at least patients with Ki-67 expression <10% might be feasible for more liberate follow-up regime after evaluation of our data in randomized, prospective and multicenter studies.
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spelling pubmed-55459172017-08-16 Increased Proliferation as Independent Predictor of Disease Recurrence in Initial Stage pTa Urothelial Bladder Cancer Breyer, Johannes Shalekenov, Sanzhar Aziz, Atiqullah van Rhijn, Bastiaan W.G. Bründl, Johannes Lausenmeyer, Eva Schäfer, Julius Denzinger, Stefan Giedl, Christian Burger, Maximilian Hartmann, Arndt Evert, Matthias Otto, Wolfgang Bladder Cancer Research Report OBJECTIVES: To investigate the predictive impact of the proliferation biomarker Ki-67 on the clinical course of patients with initial stage pTa urothelial carcinoma of the bladder (UCB). METHODS: We retrospectively analyzed all patients treated by transurethral resection of bladder tumors (TUR-B) for UCB between 1992–2004 in a single-center. Disease recurrence (≥pTa UCB) and absent tumor in histopathology, assessed by TUR-B with a non-malignant result for endoscopic suspect bladder lesion displayed endpoints. Immunohistochemical (IHC) analysis of formalin-fixed and paraffin-embedded tissue blocks was performed with an immunostainer using a primary antibody for Ki-67. Semiquantitative evaluation of Ki-67 was performed by three reviewers. Increased proliferation was defined with a cut-off value of ≥50%. Uni- and multivariable binary regression analyses were applied to address prediction of disease recurrence. RESULTS: 215 patients (84% male, median age 69 years at first diagnosis) were evaluable and included to the study. 89 patients stayed disease-free (41%), 126 patients showed recurrence (59%). Recurrence rates of patients with Ki-67 expression <10%, 10–24%, 25–49% and ≥50% were 14.8% vs. 30.8% vs. 63.9% and 80.7%, respectively (p < 0.001). In Kaplan-Meier analysis patients with increased proliferation ≥50% showed a statistically significant worse 10-year recurrence-free survival (19% vs. 57%, p < 0.001). Multivariable regression analysis revealed instillation treatment (p = 0.001) and high proliferation of Ki-67 (p < 0.001) to be independent predictors of recurrence in stage pTa UCB. CONCLUSIONS: High proliferation with Ki-67 expression ≥50% was strongly associated with worse recurrence-free survival in patients with initial stage pTa UCB. Stage pTa UCB patients with increased Ki-67 expression should undergo a strictly follow-up regime comparable to stage pT1 bladder carcinoma, while at least patients with Ki-67 expression <10% might be feasible for more liberate follow-up regime after evaluation of our data in randomized, prospective and multicenter studies. IOS Press 2017-07-27 /pmc/articles/PMC5545917/ /pubmed/28824945 http://dx.doi.org/10.3233/BLC-170103 Text en © 2017 – IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Report
Breyer, Johannes
Shalekenov, Sanzhar
Aziz, Atiqullah
van Rhijn, Bastiaan W.G.
Bründl, Johannes
Lausenmeyer, Eva
Schäfer, Julius
Denzinger, Stefan
Giedl, Christian
Burger, Maximilian
Hartmann, Arndt
Evert, Matthias
Otto, Wolfgang
Increased Proliferation as Independent Predictor of Disease Recurrence in Initial Stage pTa Urothelial Bladder Cancer
title Increased Proliferation as Independent Predictor of Disease Recurrence in Initial Stage pTa Urothelial Bladder Cancer
title_full Increased Proliferation as Independent Predictor of Disease Recurrence in Initial Stage pTa Urothelial Bladder Cancer
title_fullStr Increased Proliferation as Independent Predictor of Disease Recurrence in Initial Stage pTa Urothelial Bladder Cancer
title_full_unstemmed Increased Proliferation as Independent Predictor of Disease Recurrence in Initial Stage pTa Urothelial Bladder Cancer
title_short Increased Proliferation as Independent Predictor of Disease Recurrence in Initial Stage pTa Urothelial Bladder Cancer
title_sort increased proliferation as independent predictor of disease recurrence in initial stage pta urothelial bladder cancer
topic Research Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545917/
https://www.ncbi.nlm.nih.gov/pubmed/28824945
http://dx.doi.org/10.3233/BLC-170103
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