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NECTIN4 Expression in Extramammary Paget’s Disease: Implication of a New Therapeutic Target
Extramammary Paget’s disease (EMPD) is a rare skin cancer arising in the anogenital area. Most EMPD tumors remain dormant as in situ lesions, but the outcomes of patients with metastatic EMPD are poor because of the lack of effective systemic therapies. Nectin cell adhesion molecule 4 (NECTIN4) has...
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/PMC7460664/ https://www.ncbi.nlm.nih.gov/pubmed/32824340 http://dx.doi.org/10.3390/ijms21165891 |
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author | Murata, Maho Ito, Takamichi Tanaka, Yuka Kaku-Ito, Yumiko Furue, Masutaka |
author_facet | Murata, Maho Ito, Takamichi Tanaka, Yuka Kaku-Ito, Yumiko Furue, Masutaka |
author_sort | Murata, Maho |
collection | PubMed |
description | Extramammary Paget’s disease (EMPD) is a rare skin cancer arising in the anogenital area. Most EMPD tumors remain dormant as in situ lesions, but the outcomes of patients with metastatic EMPD are poor because of the lack of effective systemic therapies. Nectin cell adhesion molecule 4 (NECTIN4) has attracted attention as a potential therapeutic target for some cancers. Urothelial cancer is one such cancer, and clinical trials of enfortumab vedotin, a drug-conjugated anti-NECTIN4 antibody, are ongoing. However, little is known regarding the role of NECTIN4 in EMPD. In this study, we conducted immunohistochemical analysis of NECTIN4 expression in 110 clinical EMPD samples and normal skin tissue. In normal skin, positive signals were observed in epidermal keratinocytes (particularly in the lower part of the epidermis), eccrine and apocrine sweat glands, inner and outer root sheaths, and matrix of the hair follicles. The most EMPD lesions exhibited strong NECTIN4 expression, and high NECTIN4 expression was significantly associated with increased tumor thickness, advanced TNM stage, and worse disease-specific survival. These results support the potential use of NECTIN4-targeted therapy for EMPD. Our report contributes to the better understanding of the pathobiology of NECTIN4 in the skin and the skin-related adverse effects of NECTIN4-targeted therapy. |
format | Online Article Text |
id | pubmed-7460664 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74606642020-09-03 NECTIN4 Expression in Extramammary Paget’s Disease: Implication of a New Therapeutic Target Murata, Maho Ito, Takamichi Tanaka, Yuka Kaku-Ito, Yumiko Furue, Masutaka Int J Mol Sci Article Extramammary Paget’s disease (EMPD) is a rare skin cancer arising in the anogenital area. Most EMPD tumors remain dormant as in situ lesions, but the outcomes of patients with metastatic EMPD are poor because of the lack of effective systemic therapies. Nectin cell adhesion molecule 4 (NECTIN4) has attracted attention as a potential therapeutic target for some cancers. Urothelial cancer is one such cancer, and clinical trials of enfortumab vedotin, a drug-conjugated anti-NECTIN4 antibody, are ongoing. However, little is known regarding the role of NECTIN4 in EMPD. In this study, we conducted immunohistochemical analysis of NECTIN4 expression in 110 clinical EMPD samples and normal skin tissue. In normal skin, positive signals were observed in epidermal keratinocytes (particularly in the lower part of the epidermis), eccrine and apocrine sweat glands, inner and outer root sheaths, and matrix of the hair follicles. The most EMPD lesions exhibited strong NECTIN4 expression, and high NECTIN4 expression was significantly associated with increased tumor thickness, advanced TNM stage, and worse disease-specific survival. These results support the potential use of NECTIN4-targeted therapy for EMPD. Our report contributes to the better understanding of the pathobiology of NECTIN4 in the skin and the skin-related adverse effects of NECTIN4-targeted therapy. MDPI 2020-08-16 /pmc/articles/PMC7460664/ /pubmed/32824340 http://dx.doi.org/10.3390/ijms21165891 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 Murata, Maho Ito, Takamichi Tanaka, Yuka Kaku-Ito, Yumiko Furue, Masutaka NECTIN4 Expression in Extramammary Paget’s Disease: Implication of a New Therapeutic Target |
title | NECTIN4 Expression in Extramammary Paget’s Disease: Implication of a New Therapeutic Target |
title_full | NECTIN4 Expression in Extramammary Paget’s Disease: Implication of a New Therapeutic Target |
title_fullStr | NECTIN4 Expression in Extramammary Paget’s Disease: Implication of a New Therapeutic Target |
title_full_unstemmed | NECTIN4 Expression in Extramammary Paget’s Disease: Implication of a New Therapeutic Target |
title_short | NECTIN4 Expression in Extramammary Paget’s Disease: Implication of a New Therapeutic Target |
title_sort | nectin4 expression in extramammary paget’s disease: implication of a new therapeutic target |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460664/ https://www.ncbi.nlm.nih.gov/pubmed/32824340 http://dx.doi.org/10.3390/ijms21165891 |
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