Reduced p63 expression is linked to unfavourable prognosis in muscle‐invasive urothelial carcinoma of the bladder
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
Affiliations
Kira Furlano
Department of Urology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin Germany
Henning Plage
Department of Urology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin Germany
Sebastian Hofbauer
Department of Urology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin Germany
Sarah Weinberger
Department of Urology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin Germany
Bernhard Ralla
Department of Urology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin Germany
Annika Fendler
Department of Urology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin Germany
Florian Roßner
Institute of Pathology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin Germany
Simon Schallenberg
Institute of Pathology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin Germany
Sefer Elezkurtaj
Institute of Pathology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin Germany
Martina Kluth
Institute of Pathology University Medical Center Hamburg‐Eppendorf Hamburg Germany
Maximilian Lennartz
Institute of Pathology University Medical Center Hamburg‐Eppendorf Hamburg Germany
Niclas C. Blessin
Institute of Pathology University Medical Center Hamburg‐Eppendorf Hamburg Germany
Andreas H. Marx
Department of Pathology Academic Hospital Fuerth Fuerth Germany
Henrik Samtleben
Department of Pathology Academic Hospital Fuerth Fuerth Germany
Margit Fisch
Department of Urology University Medical Center Hamburg‐Eppendorf Hamburg Germany
Michael Rink
Department of Urology Marienhospital Hamburg Hamburg Germany
Marcin Slojewski
Department of Urology and Urological Oncology Pomeranian Medical University Szczecin Poland
Krystian Kaczmarek
Department of Urology and Urological Oncology Pomeranian Medical University Szczecin Poland
Thorsten Ecke
Department of Urology Helios Hospital Bad Saarow Bad Saarow Germany
Stefan Koch
Department of Pathology Helios Hospital Bad Saarow Bad Saarow Germany
Nico Adamini
Department of Urology Albertinen Hospital Hamburg Germany
Sarah Minner
Institute of Pathology University Medical Center Hamburg‐Eppendorf Hamburg Germany
Ronald Simon
Institute of Pathology University Medical Center Hamburg‐Eppendorf Hamburg Germany
Guido Sauter
Institute of Pathology University Medical Center Hamburg‐Eppendorf Hamburg Germany
Joachim Weischenfeldt
Department of Urology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin Germany
Tobias Klatte
Department of Urology Helios Hospital Bad Saarow Bad Saarow Germany
Thorsten Schlomm
Department of Urology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin Germany
David Horst
Institute of Pathology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin Germany
Henrik Zecha
Department of Urology Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin and Berlin Institute of Health Berlin Germany
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.
