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RIPK3 and AXL Expression Study in Primary Cutaneous Melanoma Unmasks AXL as Predictor of Sentinel Node Metastasis: A Pilot Study

Malignant melanoma (MM) is the most lethal skin cancer. AXL is a tyrosine kinase receptor involved in several oncogenic processes and might play a role in blocking necroptosis (a regulated cell death mechanism) in MM through the downregulation of the necroptotic-related driver RIPK3. The aim of this...

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Autores principales: Nicolè, Lorenzo, Cappello, Filippo, Cappellesso, Rocco, Piccin, Luisa, Ventura, Laura, Guzzardo, Vincenza, Del Fiore, Paolo, Chiarion-Sileni, Vanna, Dei Tos, Angelo Paolo, Mocellin, Simone, Fassina, Ambrogio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566987/
https://www.ncbi.nlm.nih.gov/pubmed/34745951
http://dx.doi.org/10.3389/fonc.2021.728319
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author Nicolè, Lorenzo
Cappello, Filippo
Cappellesso, Rocco
Piccin, Luisa
Ventura, Laura
Guzzardo, Vincenza
Del Fiore, Paolo
Chiarion-Sileni, Vanna
Dei Tos, Angelo Paolo
Mocellin, Simone
Fassina, Ambrogio
author_facet Nicolè, Lorenzo
Cappello, Filippo
Cappellesso, Rocco
Piccin, Luisa
Ventura, Laura
Guzzardo, Vincenza
Del Fiore, Paolo
Chiarion-Sileni, Vanna
Dei Tos, Angelo Paolo
Mocellin, Simone
Fassina, Ambrogio
author_sort Nicolè, Lorenzo
collection PubMed
description Malignant melanoma (MM) is the most lethal skin cancer. AXL is a tyrosine kinase receptor involved in several oncogenic processes and might play a role in blocking necroptosis (a regulated cell death mechanism) in MM through the downregulation of the necroptotic-related driver RIPK3. The aim of this study was to evaluate the clinical impact of the expression of AXL and RIPK3 in 108 primary cutaneous MMs. Association between AXL and RIPK3 immunoreactivity and clinical–pathological variables, sentinel lymph node status, and tumor-infiltrating lymphocytes (TILs) was assessed. Immunoreaction in tumor cells was detected in 30 cases (28%; range, 5%–80%) and in 17 cases (16%; range, 5%–50%) for AXL and RIPK3, respectively. Metastases in the sentinel lymph nodes were detected in 14 out of 61 patients, and these were associated with AXL-positive immunoreactivity in the primary tumor (p < 0.0001). No association between AXL and TILs was found. RIPK3 immunoreactivity was not associated with any variables. A final logistic regression analysis showed Breslow and AXL-positive immunoreactivity as the stronger predictor for positive sentinel node status [area under the receiver operating characteristic curve (AUC) of 0.96]. AXL could be a potential new biomarker for MM risk assessment, and it deserves to be further investigated in larger studies.
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spelling pubmed-85669872021-11-05 RIPK3 and AXL Expression Study in Primary Cutaneous Melanoma Unmasks AXL as Predictor of Sentinel Node Metastasis: A Pilot Study Nicolè, Lorenzo Cappello, Filippo Cappellesso, Rocco Piccin, Luisa Ventura, Laura Guzzardo, Vincenza Del Fiore, Paolo Chiarion-Sileni, Vanna Dei Tos, Angelo Paolo Mocellin, Simone Fassina, Ambrogio Front Oncol Oncology Malignant melanoma (MM) is the most lethal skin cancer. AXL is a tyrosine kinase receptor involved in several oncogenic processes and might play a role in blocking necroptosis (a regulated cell death mechanism) in MM through the downregulation of the necroptotic-related driver RIPK3. The aim of this study was to evaluate the clinical impact of the expression of AXL and RIPK3 in 108 primary cutaneous MMs. Association between AXL and RIPK3 immunoreactivity and clinical–pathological variables, sentinel lymph node status, and tumor-infiltrating lymphocytes (TILs) was assessed. Immunoreaction in tumor cells was detected in 30 cases (28%; range, 5%–80%) and in 17 cases (16%; range, 5%–50%) for AXL and RIPK3, respectively. Metastases in the sentinel lymph nodes were detected in 14 out of 61 patients, and these were associated with AXL-positive immunoreactivity in the primary tumor (p < 0.0001). No association between AXL and TILs was found. RIPK3 immunoreactivity was not associated with any variables. A final logistic regression analysis showed Breslow and AXL-positive immunoreactivity as the stronger predictor for positive sentinel node status [area under the receiver operating characteristic curve (AUC) of 0.96]. AXL could be a potential new biomarker for MM risk assessment, and it deserves to be further investigated in larger studies. Frontiers Media S.A. 2021-10-21 /pmc/articles/PMC8566987/ /pubmed/34745951 http://dx.doi.org/10.3389/fonc.2021.728319 Text en Copyright © 2021 Nicolè, Cappello, Cappellesso, Piccin, Ventura, Guzzardo, Del Fiore, Chiarion-Sileni, Dei Tos, Mocellin and Fassina https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Nicolè, Lorenzo
Cappello, Filippo
Cappellesso, Rocco
Piccin, Luisa
Ventura, Laura
Guzzardo, Vincenza
Del Fiore, Paolo
Chiarion-Sileni, Vanna
Dei Tos, Angelo Paolo
Mocellin, Simone
Fassina, Ambrogio
RIPK3 and AXL Expression Study in Primary Cutaneous Melanoma Unmasks AXL as Predictor of Sentinel Node Metastasis: A Pilot Study
title RIPK3 and AXL Expression Study in Primary Cutaneous Melanoma Unmasks AXL as Predictor of Sentinel Node Metastasis: A Pilot Study
title_full RIPK3 and AXL Expression Study in Primary Cutaneous Melanoma Unmasks AXL as Predictor of Sentinel Node Metastasis: A Pilot Study
title_fullStr RIPK3 and AXL Expression Study in Primary Cutaneous Melanoma Unmasks AXL as Predictor of Sentinel Node Metastasis: A Pilot Study
title_full_unstemmed RIPK3 and AXL Expression Study in Primary Cutaneous Melanoma Unmasks AXL as Predictor of Sentinel Node Metastasis: A Pilot Study
title_short RIPK3 and AXL Expression Study in Primary Cutaneous Melanoma Unmasks AXL as Predictor of Sentinel Node Metastasis: A Pilot Study
title_sort ripk3 and axl expression study in primary cutaneous melanoma unmasks axl as predictor of sentinel node metastasis: a pilot study
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566987/
https://www.ncbi.nlm.nih.gov/pubmed/34745951
http://dx.doi.org/10.3389/fonc.2021.728319
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