Human skin biomarkers relationship to response to treatment with tyrosine kinase inhibitors in advanced EGFR‐mutated lung adenocarcinoma

Background A relationship between the EGFR signaling pathway expression in skin and the use of targeted cancer therapies has been previously demonstrated. Consistent evidence to support the use of skin biopsies as a surrogate for therapeutic evaluation is needed. The purpose of this study was to est...

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Main Authors: Anahí Castañeda‐Zárraga, Jerónimo Rafael Rodríguez‐Cid, Rodrigo Rafael Flores‐Mariñelarena, Héctor Trinidad‐Bibiano, José Fabián Martínez‐Herrera, Carla Paola Sánchez‐Ríos, Valeria Michelle Fernández‐Garibay, Jorge Arturo Alatorre‐Alexander, Luis Martínez‐Barrera, Patricio Javier Santillán‐Doherty, María Elisa Vega‐Memije
Format: Article
Language:English
Published: Wiley 2020-11-01
Series:Thoracic Cancer
Subjects:
Online Access:https://doi.org/10.1111/1759-7714.13657
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spelling doaj-35e073c0e5c649ada44cd7681096023f2020-11-25T03:40:45ZengWileyThoracic Cancer1759-77061759-77142020-11-0111113243325110.1111/1759-7714.13657Human skin biomarkers relationship to response to treatment with tyrosine kinase inhibitors in advanced EGFR‐mutated lung adenocarcinomaAnahí Castañeda‐Zárraga0Jerónimo Rafael Rodríguez‐Cid1Rodrigo Rafael Flores‐Mariñelarena2Héctor Trinidad‐Bibiano3José Fabián Martínez‐Herrera4Carla Paola Sánchez‐Ríos5Valeria Michelle Fernández‐Garibay6Jorge Arturo Alatorre‐Alexander7Luis Martínez‐Barrera8Patricio Javier Santillán‐Doherty9María Elisa Vega‐Memije10Department of Dermatology Hospital General Dr. Manuel Gea Gónzalez Mexico City MexicoDepartment of Oncology Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas Mexico City MexicoDepartment of Internal Medicine Fundación Clínica Médica Sur Mexico City MexicoDepartment of Pathology Hospital General Dr. Manuel Gea Gónzalez Mexico City MexicoDepartment of Oncology Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas Mexico City MexicoDepartment of Oncology Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas Mexico City MexicoSchool of Medicine Monterrey Institute of Technology and Higher Education Mexico City MexicoDepartment of Oncology Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas Mexico City MexicoDepartment of Oncology Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas Mexico City MexicoInstituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas Mexico City MexicoDepartment of Dermatology Hospital General Dr. Manuel Gea Gónzalez Mexico City MexicoBackground A relationship between the EGFR signaling pathway expression in skin and the use of targeted cancer therapies has been previously demonstrated. Consistent evidence to support the use of skin biopsies as a surrogate for therapeutic evaluation is needed. The purpose of this study was to establish the relationship between the expression of EGFR signaling pathway markers in skin samples from EGFR‐mutated metastatic lung adenocarcinoma patients and their response to tyrosine kinase inhibitors. Methods This was a prospective single blind analysis of 35 skin biopsies from 31 patients with confirmed advanced EGFR‐mutated lung adenocarcinoma. Immunohistochemistry was performed: EGFR, p27, Ki67, STAT3 and MAPK, as well as H&E histopathological analysis, in order to determine their treatment response to tyrosine kinase inhibitors. Results EGFR, Ki67, STAT3, stratum corneum thickness (number of layers and millimeters) from skin samples had a statistical correlation with an adequate treatment response (P = 0.025, 0.015, 0.017, 0.041, 0.039 respectively). EGFR, p27 and number of layers of the stratum corneum were related to a better median progression‐free survival (P = 0.025 and P = 0.030). Conclusions The relationship between EGFR pathway inhibition in the skin and oncological outcomes obtained explains the parallel biological effects of tyrosine kinase inhibitors. We hope that our work incites future research to help validate and assess the use of these markers as potential prognostic and predictive factors.https://doi.org/10.1111/1759-7714.13657BiomarkersEGFRNSCLCskin biopsy
collection DOAJ
language English
format Article
sources DOAJ
author Anahí Castañeda‐Zárraga
Jerónimo Rafael Rodríguez‐Cid
Rodrigo Rafael Flores‐Mariñelarena
Héctor Trinidad‐Bibiano
José Fabián Martínez‐Herrera
Carla Paola Sánchez‐Ríos
Valeria Michelle Fernández‐Garibay
Jorge Arturo Alatorre‐Alexander
Luis Martínez‐Barrera
Patricio Javier Santillán‐Doherty
María Elisa Vega‐Memije
spellingShingle Anahí Castañeda‐Zárraga
Jerónimo Rafael Rodríguez‐Cid
Rodrigo Rafael Flores‐Mariñelarena
Héctor Trinidad‐Bibiano
José Fabián Martínez‐Herrera
Carla Paola Sánchez‐Ríos
Valeria Michelle Fernández‐Garibay
Jorge Arturo Alatorre‐Alexander
Luis Martínez‐Barrera
Patricio Javier Santillán‐Doherty
María Elisa Vega‐Memije
Human skin biomarkers relationship to response to treatment with tyrosine kinase inhibitors in advanced EGFR‐mutated lung adenocarcinoma
Thoracic Cancer
Biomarkers
EGFR
NSCLC
skin biopsy
author_facet Anahí Castañeda‐Zárraga
Jerónimo Rafael Rodríguez‐Cid
Rodrigo Rafael Flores‐Mariñelarena
Héctor Trinidad‐Bibiano
José Fabián Martínez‐Herrera
Carla Paola Sánchez‐Ríos
Valeria Michelle Fernández‐Garibay
Jorge Arturo Alatorre‐Alexander
Luis Martínez‐Barrera
Patricio Javier Santillán‐Doherty
María Elisa Vega‐Memije
author_sort Anahí Castañeda‐Zárraga
title Human skin biomarkers relationship to response to treatment with tyrosine kinase inhibitors in advanced EGFR‐mutated lung adenocarcinoma
title_short Human skin biomarkers relationship to response to treatment with tyrosine kinase inhibitors in advanced EGFR‐mutated lung adenocarcinoma
title_full Human skin biomarkers relationship to response to treatment with tyrosine kinase inhibitors in advanced EGFR‐mutated lung adenocarcinoma
title_fullStr Human skin biomarkers relationship to response to treatment with tyrosine kinase inhibitors in advanced EGFR‐mutated lung adenocarcinoma
title_full_unstemmed Human skin biomarkers relationship to response to treatment with tyrosine kinase inhibitors in advanced EGFR‐mutated lung adenocarcinoma
title_sort human skin biomarkers relationship to response to treatment with tyrosine kinase inhibitors in advanced egfr‐mutated lung adenocarcinoma
publisher Wiley
series Thoracic Cancer
issn 1759-7706
1759-7714
publishDate 2020-11-01
description Background A relationship between the EGFR signaling pathway expression in skin and the use of targeted cancer therapies has been previously demonstrated. Consistent evidence to support the use of skin biopsies as a surrogate for therapeutic evaluation is needed. The purpose of this study was to establish the relationship between the expression of EGFR signaling pathway markers in skin samples from EGFR‐mutated metastatic lung adenocarcinoma patients and their response to tyrosine kinase inhibitors. Methods This was a prospective single blind analysis of 35 skin biopsies from 31 patients with confirmed advanced EGFR‐mutated lung adenocarcinoma. Immunohistochemistry was performed: EGFR, p27, Ki67, STAT3 and MAPK, as well as H&E histopathological analysis, in order to determine their treatment response to tyrosine kinase inhibitors. Results EGFR, Ki67, STAT3, stratum corneum thickness (number of layers and millimeters) from skin samples had a statistical correlation with an adequate treatment response (P = 0.025, 0.015, 0.017, 0.041, 0.039 respectively). EGFR, p27 and number of layers of the stratum corneum were related to a better median progression‐free survival (P = 0.025 and P = 0.030). Conclusions The relationship between EGFR pathway inhibition in the skin and oncological outcomes obtained explains the parallel biological effects of tyrosine kinase inhibitors. We hope that our work incites future research to help validate and assess the use of these markers as potential prognostic and predictive factors.
topic Biomarkers
EGFR
NSCLC
skin biopsy
url https://doi.org/10.1111/1759-7714.13657
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