Loss of Upk1a and Upk1b expression is linked to stage progression in urothelial carcinoma of the bladder

Krystian Kaczmarek, Henning Plage, Kira Furlano, Sebastian Hofbauer, Sarah Weinberger, Bernhard Ralla, Antonia Franz, Annika Fendler, Michela de Martino, Florian Roßner, Simon Schallenberg, Sefer Elezkurtaj, Martina Kluth, Maximilian Lennartz, Niclas C Blessin, Andreas H Marx, Henrik Samtleben, Margit Fisch, Michael Rink, Marcin SlojewskiThorsten Ecke, Steffen Hallmann, Stefan Koch, Nico Adamini, Sarah Minner, Ronald Simon*, Guido Sauter, Joachim Weischenfeldt, Tobias Klatte, Thorsten Schlomm, David Horst, Henrik Zecha

*Corresponding author af dette arbejde

Abstract

BACKGROUND: Uroplakin-1a (Upk1a) and uroplakin-1b (Upk1b) have recently been identified as diagnostic markers for the distinction of urothelial carcinomas from other solid tumor entities. Both proteins play an important role in the stabilization and strengthening of epithelial cells that line the bladder.

METHODS: To evaluate the prognostic role of uroplakin expression in urothelial carcinomas, more than 2700 urothelial neoplasms were analyzed in a tissue microarray format by immunohistochemistry. To further assess the diagnostic role of uroplakin immunohistochemistry, results were compared with preexisting GATA3 data.

RESULT: The fraction of Upk1a/Upk1b positive cases decreased slightly from pTaG2 low-grade (88% positive for Upk1a/87% positive for Upk1b) and pTaG2 high-grade (92%/89%) to pTaG3 (83%/88%; p > 0.05) and was lower in muscle-invasive (pT2-4) carcinomas (42%/64%; p < 0.0001/p < 0.0001 for pTa vs. pT2-4). Within pT2-4 carcinomas, high expression of Upk1a and Upk1b was linked to nodal metastasis and lymphatic vessel infiltration (p < 0.05) but unrelated to patient outcome. There were significant associations between Upk1a, Upk1b and GATA3 immunostaining (p < 0.0001 each), but 11% of GATA3 negative cancers were Upk1a/b positive and 8% of Upk1a/b negative cancers were GATA3 positive. Absence of GATA3/Upk1a/b staining was significantly linked to poor patient survival in the subgroup of 126 pT4 carcinomas (p = 0.0004) but not in pT2 and pT3 cancers.

CONCLUSIONS: In summary, the results of our study demonstrate that Upk1a and/or Upk1b immunohistochemistry can complement GATA3 for the distinction of urothelial carcinomas. Furthermore, a progressive loss of Upk1a/b expression during stage progression and a prognostic role of the combination GATA3/Upk1a/Upk1b in pT4 carcinomas is evident.

OriginalsprogEngelsk
TidsskriftInternational Urology and Nephrology
Vol/bind56
Udgave nummer2
Sider (fra-til)499-508
Antal sider10
ISSN0301-1623
DOI
StatusUdgivet - feb. 2024

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