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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...

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Autores principales: Murata, Maho, Ito, Takamichi, Tanaka, Yuka, Kaku-Ito, Yumiko, Furue, Masutaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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