Reduced p63 expression is linked to unfavourable prognosis in muscle‐invasive urothelial carcinoma of the bladder
Abstract Objective There is a shortage of established prognostic biomarkers in bladder cancer. One candidate is tumour protein 63 (p63), a transcription factor of the p53 gene family that is expressed in the normal urothelium. Recently proposed RNA expression‐based molecular classifiers of bladder c...
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Wiley
2024-11-01
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| Online Access: | https://doi.org/10.1002/bco2.431 |
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| author | Kira Furlano Henning Plage Sebastian Hofbauer Sarah Weinberger Bernhard Ralla Annika Fendler Florian Roßner Simon Schallenberg Sefer Elezkurtaj Martina Kluth Maximilian Lennartz Niclas C. Blessin Andreas H. Marx Henrik Samtleben Margit Fisch Michael Rink Marcin Slojewski Krystian Kaczmarek Thorsten Ecke Stefan Koch Nico Adamini Sarah Minner Ronald Simon Guido Sauter Joachim Weischenfeldt Tobias Klatte Thorsten Schlomm David Horst Henrik Zecha |
| author_facet | Kira Furlano Henning Plage Sebastian Hofbauer Sarah Weinberger Bernhard Ralla Annika Fendler Florian Roßner Simon Schallenberg Sefer Elezkurtaj Martina Kluth Maximilian Lennartz Niclas C. Blessin Andreas H. Marx Henrik Samtleben Margit Fisch Michael Rink Marcin Slojewski Krystian Kaczmarek Thorsten Ecke Stefan Koch Nico Adamini Sarah Minner Ronald Simon Guido Sauter Joachim Weischenfeldt Tobias Klatte Thorsten Schlomm David Horst Henrik Zecha |
| author_sort | Kira Furlano |
| collection | DOAJ |
| description | Abstract Objective There is a shortage of established prognostic biomarkers in bladder cancer. One candidate is tumour protein 63 (p63), a transcription factor of the p53 gene family that is expressed in the normal urothelium. Recently proposed RNA expression‐based molecular classifiers of bladder cancer identified high p63 expression as a component of a basal/squamous subtype linked to poor patient prognosis. Methods In this study, p63 protein expression was analysed by immunohistochemistry on more than 2500 urothelial bladder carcinomas in a tissue microarray format to determine its relationship with clinicopathological parameters of disease progression and patient outcome. Results Nuclear p63 staining was seen in all cells of normal urothelium and at elevated levels in pTaG2 tumours. The rate of p63 positive cases and the staining intensity was lower in pTaG3 tumours (93.2%, p < 0.0001 for pTaG3 vs. pTaG2) and markedly lower in pT2‐4 carcinomas (83.5%, p = 0.0120 for pT2‐4 vs. pTaG3). Within 1018 pT2‐4 carcinomas treated by cystectomy, low p63 expression was linked to nodal metastasis (p = 0.0028) and overall survival (p = 0.0005). The association with survival was independent of pT and pN (p = 0.0081). p63 expression was associated with GATA3 expression (p < 0.0001), a luminal cell type marker associated with favourable disease. A joint analysis of p63 and GATA3 did not suggest that GATA3 could provide additional prognostic information. Conclusion The independent prognostic role of reduced p63 expression in advanced urothelial carcinomas suggests that p63 could be a useful biomarker to distinguish pT2‐4 urothelial carcinomas. |
| format | Article |
| id | doaj-art-858134d5041e486092630ed50c6fad55 |
| institution | Kabale University |
| issn | 2688-4526 |
| language | English |
| publishDate | 2024-11-01 |
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| spelling | doaj-art-858134d5041e486092630ed50c6fad552025-01-22T02:21:03ZengWileyBJUI Compass2688-45262024-11-015111195120310.1002/bco2.431Reduced p63 expression is linked to unfavourable prognosis in muscle‐invasive urothelial carcinoma of the bladderKira Furlano0Henning Plage1Sebastian Hofbauer2Sarah Weinberger3Bernhard Ralla4Annika Fendler5Florian Roßner6Simon Schallenberg7Sefer Elezkurtaj8Martina Kluth9Maximilian Lennartz10Niclas C. Blessin11Andreas H. Marx12Henrik Samtleben13Margit Fisch14Michael Rink15Marcin Slojewski16Krystian Kaczmarek17Thorsten Ecke18Stefan Koch19Nico Adamini20Sarah Minner21Ronald Simon22Guido Sauter23Joachim Weischenfeldt24Tobias Klatte25Thorsten Schlomm26David Horst27Henrik Zecha28Department of Urology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin GermanyDepartment of Urology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin GermanyDepartment of Urology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin GermanyDepartment of Urology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin GermanyDepartment of Urology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin GermanyDepartment of Urology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin GermanyInstitute of Pathology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin GermanyInstitute of Pathology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin GermanyInstitute of Pathology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin GermanyInstitute of Pathology University Medical Center Hamburg‐Eppendorf Hamburg GermanyInstitute of Pathology University Medical Center Hamburg‐Eppendorf Hamburg GermanyInstitute of Pathology University Medical Center Hamburg‐Eppendorf Hamburg GermanyDepartment of Pathology Academic Hospital Fuerth Fuerth GermanyDepartment of Pathology Academic Hospital Fuerth Fuerth GermanyDepartment of Urology University Medical Center Hamburg‐Eppendorf Hamburg GermanyDepartment of Urology Marienhospital Hamburg Hamburg GermanyDepartment of Urology and Urological Oncology Pomeranian Medical University Szczecin PolandDepartment of Urology and Urological Oncology Pomeranian Medical University Szczecin PolandDepartment of Urology Helios Hospital Bad Saarow Bad Saarow GermanyDepartment of Pathology Helios Hospital Bad Saarow Bad Saarow GermanyDepartment of Urology Albertinen Hospital Hamburg GermanyInstitute of Pathology University Medical Center Hamburg‐Eppendorf Hamburg GermanyInstitute of Pathology University Medical Center Hamburg‐Eppendorf Hamburg GermanyInstitute of Pathology University Medical Center Hamburg‐Eppendorf Hamburg GermanyDepartment of Urology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin GermanyDepartment of Urology Helios Hospital Bad Saarow Bad Saarow GermanyDepartment of Urology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin GermanyInstitute of Pathology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin GermanyDepartment of Urology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin GermanyAbstract Objective There is a shortage of established prognostic biomarkers in bladder cancer. One candidate is tumour protein 63 (p63), a transcription factor of the p53 gene family that is expressed in the normal urothelium. Recently proposed RNA expression‐based molecular classifiers of bladder cancer identified high p63 expression as a component of a basal/squamous subtype linked to poor patient prognosis. Methods In this study, p63 protein expression was analysed by immunohistochemistry on more than 2500 urothelial bladder carcinomas in a tissue microarray format to determine its relationship with clinicopathological parameters of disease progression and patient outcome. Results Nuclear p63 staining was seen in all cells of normal urothelium and at elevated levels in pTaG2 tumours. The rate of p63 positive cases and the staining intensity was lower in pTaG3 tumours (93.2%, p < 0.0001 for pTaG3 vs. pTaG2) and markedly lower in pT2‐4 carcinomas (83.5%, p = 0.0120 for pT2‐4 vs. pTaG3). Within 1018 pT2‐4 carcinomas treated by cystectomy, low p63 expression was linked to nodal metastasis (p = 0.0028) and overall survival (p = 0.0005). The association with survival was independent of pT and pN (p = 0.0081). p63 expression was associated with GATA3 expression (p < 0.0001), a luminal cell type marker associated with favourable disease. A joint analysis of p63 and GATA3 did not suggest that GATA3 could provide additional prognostic information. Conclusion The independent prognostic role of reduced p63 expression in advanced urothelial carcinomas suggests that p63 could be a useful biomarker to distinguish pT2‐4 urothelial carcinomas.https://doi.org/10.1002/bco2.431biomarkerimmunohistochemistryp63tissue microarrayurothelial carcinoma |
| spellingShingle | Kira Furlano Henning Plage Sebastian Hofbauer Sarah Weinberger Bernhard Ralla Annika Fendler Florian Roßner Simon Schallenberg Sefer Elezkurtaj Martina Kluth Maximilian Lennartz Niclas C. Blessin Andreas H. Marx Henrik Samtleben Margit Fisch Michael Rink Marcin Slojewski Krystian Kaczmarek Thorsten Ecke Stefan Koch Nico Adamini Sarah Minner Ronald Simon Guido Sauter Joachim Weischenfeldt Tobias Klatte Thorsten Schlomm David Horst Henrik Zecha Reduced p63 expression is linked to unfavourable prognosis in muscle‐invasive urothelial carcinoma of the bladder BJUI Compass biomarker immunohistochemistry p63 tissue microarray urothelial carcinoma |
| title | Reduced p63 expression is linked to unfavourable prognosis in muscle‐invasive urothelial carcinoma of the bladder |
| title_full | Reduced p63 expression is linked to unfavourable prognosis in muscle‐invasive urothelial carcinoma of the bladder |
| title_fullStr | Reduced p63 expression is linked to unfavourable prognosis in muscle‐invasive urothelial carcinoma of the bladder |
| title_full_unstemmed | Reduced p63 expression is linked to unfavourable prognosis in muscle‐invasive urothelial carcinoma of the bladder |
| title_short | Reduced p63 expression is linked to unfavourable prognosis in muscle‐invasive urothelial carcinoma of the bladder |
| title_sort | reduced p63 expression is linked to unfavourable prognosis in muscle invasive urothelial carcinoma of the bladder |
| topic | biomarker immunohistochemistry p63 tissue microarray urothelial carcinoma |
| url | https://doi.org/10.1002/bco2.431 |
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