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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)...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7432817 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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