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Concordance and prognostic value of antibody drug conjugate and checkpoint inhibition targets in matched bladder cancer specimens from transurethral resection of the bladder, radical cystectomy and lymphadenectomy: bladder cancer

Background - Concordance of NECTIN-4 gene and protein expression and clinic-pathologic associations in matched bladder cancer (BC) triplets, defined as histological specimens from transurethral resection of the bladder (TUR-B), radical cystectomy (RC), and lymphadenectomy (LA) from the same patient,...

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Autori principali: Uysal, Daniel (Autore) , Reible, Bruno (Autore) , Wildner, Lukas (Autore) , Steidler, Annette (Autore) , Stöth, Manuel (Autore) , Wessels, Frederik (Autore) , Nientiedt, Malin (Autore) , Worst, Thomas (Autore) , Erben, Philipp (Autore) , Hartung, Luisa (Autore) , Nitschke, Katja (Autore) , Brochhausen, Christoph (Autore) , Michel, Maurice Stephan (Autore) , Nuhn, Philipp (Autore) , Kowalewski, Karl-Friedrich (Autore)
Natura: Article (Journal)
Lingua:inglese
Pubblicazione: June 2026
In: Urologic oncology
Year: 2026, Volume: 44, Fascicolo: 6, Pages: 86-97
ISSN:1873-2496
DOI:10.1016/j.urolonc.2026.111095
Accesso online:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.urolonc.2026.111095
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S1078143926001067
Testo
Note sull'autore:Daniel Uysal, MD, Bruno Reible, MD, Lukas Wildner, MD, Annette Steidler, Manuel Stöth, MD, Frederik Wessels, MD, Malin Nientiedt, MD, Thomas Stefan Worst, MD, Philipp Erben, MD, Luisa Egen, MD, Katja Nitschke, PhD, Christoph Brochhausen, MD, Maurice Stephan Michel, MD, Philipp Nuhn, MD, Karl-Friedrich Kowalewski, MD
Descrizione
Riassunto:Background - Concordance of NECTIN-4 gene and protein expression and clinic-pathologic associations in matched bladder cancer (BC) triplets, defined as histological specimens from transurethral resection of the bladder (TUR-B), radical cystectomy (RC), and lymphadenectomy (LA) from the same patient, remains unknown. With Enfortumab Vedotin (EV) potentially moving into earlier treatment settings, understanding expression of NECTIN-4 and other targets in archival tissue samples is important. This study characterized protein expression of NECTIN-4 and gene expression of NECTIN4, TACSTD2, ERBB2, PD-L1 and PD1 in matched BC triplet specimens and correlated findings with survival endpoints. - Methods - This retrospective study analyzed NECTIN-4 protein expression and gene expression of 6 target genes using immunohistochemistry and quantitative real-time polymerase chain reaction in matched TUR-B, RC, and LA tissue samples from 27 patients with BC. NECTIN-4 was validated in 3 independent BC cohorts. Protein and gene expression were correlated with clinic-pathologic characteristics. Prognostic associations with survival were analyzed using Kaplan-Meier estimates, log-rank tests and Cox proportional hazard models. - Results - Median NECTIN-4 protein expression differed significantly across tissues types with highest levels in TUR-B, lower levels in RC, and intermediate levels in LA specimens Quantitative analysis confirmed significant differences in H-scores across specimens. Expression of NECTIN-4, TACSTD2, PD-L1 and ERBB2 varied significantly across triplets. NECTIN-4 protein expression was not associated with overall or progression-free survival, whereas NECTIN-4 gene expression showed significant but contradictory survival associations in different BC cohorts. - Conclusion - NECTIN-4 expression differs by tissue type, limiting prognostic value and supporting site-specific biomarker assessment in BC.
Descrizione del documento:Online verfügbar: 14. April 2026, Artikelversion: 7. Mai 2026
Gesehen am 02.07.2026
Descrizione fisica:Online Resource
ISSN:1873-2496
DOI:10.1016/j.urolonc.2026.111095

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