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. 2024 Sep 10;5(11):1081-1089.
doi: 10.1002/bco2.431. eCollection 2024 Nov.

Reduced p63 expression is linked to unfavourable prognosis in muscle-invasive urothelial carcinoma of the bladder

Kira Furlano  1 , Henning Plage  1 , Sebastian Hofbauer  1 , Sarah Weinberger  1 , Bernhard Ralla  1 , Annika Fendler  1 , Florian Roßner  2 , Simon Schallenberg  2 , Sefer Elezkurtaj  2 , Martina Kluth  3 , Maximilian Lennartz  3 , Niclas C Blessin  3 , Andreas H Marx  4 , Henrik Samtleben  4 , Margit Fisch  5 , Michael Rink  6 , Marcin Slojewski  7 , Krystian Kaczmarek  7 , Thorsten Ecke  8 , Stefan Koch  9 , Nico Adamini  10 , Sarah Minner  3 , Ronald Simon  3 , Guido Sauter  3 , Joachim Weischenfeldt  1   11   12 , Tobias Klatte  8 , Thorsten Schlomm  1 , David Horst  2 , Henrik Zecha  1   10
Affiliations

Reduced p63 expression is linked to unfavourable prognosis in muscle-invasive urothelial carcinoma of the bladder

Kira Furlano et al. BJUI Compass. .

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] BJUI Compass. 2024 Dec 30;5(12):1324-1329. doi: 10.1002/bco2.482. eCollection 2024 Dec. BJUI Compass. 2024. PMID: 39744071 Free PMC article.

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.

Keywords: biomarker; immunohistochemistry; p63; tissue microarray; urothelial carcinoma.

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Conflict of interest statement

The recombinant rabbit monoclonal p63 antibody, clone MSVA‐063R, was obtained from MS Validated Antibodies GmbH, Hamburg, Germany (owned by a family member of GS).

Figures

FIGURE 1
FIGURE 1
Protein 63 (p63) immunostaining in urothelial carcinomas. The panels show strong nuclear p63 staining in all cells except umbrella cells of normal urothelium (A), strong p63 staining in all cells of a low grade pTaG2 tumour (B), loss of p63 staining in most atypical cells of a urothelial carcinoma in situ (C), and loss of p63 staining in many non‐basally located tumour cells of a pTaG3 tumour (D). Samples from muscle‐invasive urothelial carcinomas show strong nuclear staining of all tumour cells (E, F), heterogeneous p63 staining predominating in basal cell layers at the invasive margin (G) and complete absence of p63 staining (H).
FIGURE 2
FIGURE 2
Protein 63 (p63) immunostaining and prognosis in muscle‐invasive urothelial carcinomas. (A) pT2‐4 carcinomas, (B) only pT2 carcinomas, (C) only pT3 carcinomas and (D) only pT4 carcinomas.
FIGURE 3
FIGURE 3
Protein 63 (p63) versus GATA3 immunostaining.
FIGURE 4
FIGURE 4
Combined protein 63 (p63) and GATA3 immunostaining and prognosis.
See this image and copyright information in PMC

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