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Expression of Nectin-4 and PD-L1 in Upper Tract Urothelial Carcinoma

Enfortumab vedotin is a novel antibody–drug conjugate targeting Nectin-4, which is highly expressed in urothelial carcinoma. However, the expression status of Nectin-4 in upper tract urothelial carcinoma (UTUC) remains unclear. The relationship between Nectin-4 and Programmed Death Ligand 1 (PD-L1)...

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Autores principales: Tomiyama, Eisuke, Fujita, Kazutoshi, Rodriguez Pena, Maria Del Carmen, Taheri, Diana, Banno, Eri, Kato, Taigo, Hatano, Koji, Kawashima, Atsunari, Ujike, Takeshi, Uemura, Motohide, Takao, Tetsuya, Yamaguchi, Seiji, Fushimi, Hiroaki, Yoshimura, Kazuhiro, Uemura, Hirotsugu, Netto, George J., Nonomura, Norio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432817/
https://www.ncbi.nlm.nih.gov/pubmed/32751328
http://dx.doi.org/10.3390/ijms21155390
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author Tomiyama, Eisuke
Fujita, Kazutoshi
Rodriguez Pena, Maria Del Carmen
Taheri, Diana
Banno, Eri
Kato, Taigo
Hatano, Koji
Kawashima, Atsunari
Ujike, Takeshi
Uemura, Motohide
Takao, Tetsuya
Yamaguchi, Seiji
Fushimi, Hiroaki
Yoshimura, Kazuhiro
Uemura, Hirotsugu
Netto, George J.
Nonomura, Norio
author_facet Tomiyama, Eisuke
Fujita, Kazutoshi
Rodriguez Pena, Maria Del Carmen
Taheri, Diana
Banno, Eri
Kato, Taigo
Hatano, Koji
Kawashima, Atsunari
Ujike, Takeshi
Uemura, Motohide
Takao, Tetsuya
Yamaguchi, Seiji
Fushimi, Hiroaki
Yoshimura, Kazuhiro
Uemura, Hirotsugu
Netto, George J.
Nonomura, Norio
author_sort Tomiyama, Eisuke
collection PubMed
description Enfortumab vedotin is a novel antibody–drug conjugate targeting Nectin-4, which is highly expressed in urothelial carcinoma. However, the expression status of Nectin-4 in upper tract urothelial carcinoma (UTUC) remains unclear. The relationship between Nectin-4 and Programmed Death Ligand 1 (PD-L1) in UTUC is also ambiguous. We performed immunohistochemical analysis of 99 UTUC tissue microarray to assess the expression of Nectin-4 and PD-L1 in UTUC. Nectin-4-positivity was detected in 65 (65.7%) samples, and PD-L1 was detected in 24 (24.2%) samples. There was no correlation between the expression of Nectin-4 and PD-L1. Patients with strong Nectin-4-expressing tumors had a significantly higher risk of progression (p = 0.031) and cancer-specific mortality (p = 0.036). Strong Nectin-4 expression was also an independent predictor of disease progression in the high-risk group (pT3 ≤ or presence of lymphovascular invasion or lymph node metastasis) (Hazard ratio, 3.32 [95% confidence interval, 1.20–7.98; p = 0.027]). In conclusion, we demonstrated that Nectin-4 expression rate in UTUC was 65.7% and independent of PD-L1 expression. Strong Nectin-4 expression was associated with worse progression-free survival in high-risk UTUC. These findings suggested that enfortumab vedotin may be effective in a broad range of patients with UTUC, regardless of PD-L1 expression.
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spelling pubmed-74328172020-08-27 Expression of Nectin-4 and PD-L1 in Upper Tract Urothelial Carcinoma Tomiyama, Eisuke Fujita, Kazutoshi Rodriguez Pena, Maria Del Carmen Taheri, Diana Banno, Eri Kato, Taigo Hatano, Koji Kawashima, Atsunari Ujike, Takeshi Uemura, Motohide Takao, Tetsuya Yamaguchi, Seiji Fushimi, Hiroaki Yoshimura, Kazuhiro Uemura, Hirotsugu Netto, George J. Nonomura, Norio Int J Mol Sci Article Enfortumab vedotin is a novel antibody–drug conjugate targeting Nectin-4, which is highly expressed in urothelial carcinoma. However, the expression status of Nectin-4 in upper tract urothelial carcinoma (UTUC) remains unclear. The relationship between Nectin-4 and Programmed Death Ligand 1 (PD-L1) in UTUC is also ambiguous. We performed immunohistochemical analysis of 99 UTUC tissue microarray to assess the expression of Nectin-4 and PD-L1 in UTUC. Nectin-4-positivity was detected in 65 (65.7%) samples, and PD-L1 was detected in 24 (24.2%) samples. There was no correlation between the expression of Nectin-4 and PD-L1. Patients with strong Nectin-4-expressing tumors had a significantly higher risk of progression (p = 0.031) and cancer-specific mortality (p = 0.036). Strong Nectin-4 expression was also an independent predictor of disease progression in the high-risk group (pT3 ≤ or presence of lymphovascular invasion or lymph node metastasis) (Hazard ratio, 3.32 [95% confidence interval, 1.20–7.98; p = 0.027]). In conclusion, we demonstrated that Nectin-4 expression rate in UTUC was 65.7% and independent of PD-L1 expression. Strong Nectin-4 expression was associated with worse progression-free survival in high-risk UTUC. These findings suggested that enfortumab vedotin may be effective in a broad range of patients with UTUC, regardless of PD-L1 expression. MDPI 2020-07-29 /pmc/articles/PMC7432817/ /pubmed/32751328 http://dx.doi.org/10.3390/ijms21155390 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tomiyama, Eisuke
Fujita, Kazutoshi
Rodriguez Pena, Maria Del Carmen
Taheri, Diana
Banno, Eri
Kato, Taigo
Hatano, Koji
Kawashima, Atsunari
Ujike, Takeshi
Uemura, Motohide
Takao, Tetsuya
Yamaguchi, Seiji
Fushimi, Hiroaki
Yoshimura, Kazuhiro
Uemura, Hirotsugu
Netto, George J.
Nonomura, Norio
Expression of Nectin-4 and PD-L1 in Upper Tract Urothelial Carcinoma
title Expression of Nectin-4 and PD-L1 in Upper Tract Urothelial Carcinoma
title_full Expression of Nectin-4 and PD-L1 in Upper Tract Urothelial Carcinoma
title_fullStr Expression of Nectin-4 and PD-L1 in Upper Tract Urothelial Carcinoma
title_full_unstemmed Expression of Nectin-4 and PD-L1 in Upper Tract Urothelial Carcinoma
title_short Expression of Nectin-4 and PD-L1 in Upper Tract Urothelial Carcinoma
title_sort expression of nectin-4 and pd-l1 in upper tract urothelial carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432817/
https://www.ncbi.nlm.nih.gov/pubmed/32751328
http://dx.doi.org/10.3390/ijms21155390
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