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Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer

The evaluation of mediastinal lymph nodes is critical for the correct staging of patients with lung cancer (LC). Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique for mediastinal staging, though unfortunately lymph node micrometastasis is...

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Autores principales: Leiro-Fernandez, Virginia, De Chiara, Loretta, Rodríguez-Girondo, Mar, Botana-Rial, Maribel, Valverde, Diana, Núñez-Delgado, Manuel, Fernández-Villar, Alberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826358/
https://www.ncbi.nlm.nih.gov/pubmed/31547177
http://dx.doi.org/10.3390/cancers11101408
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author Leiro-Fernandez, Virginia
De Chiara, Loretta
Rodríguez-Girondo, Mar
Botana-Rial, Maribel
Valverde, Diana
Núñez-Delgado, Manuel
Fernández-Villar, Alberto
author_facet Leiro-Fernandez, Virginia
De Chiara, Loretta
Rodríguez-Girondo, Mar
Botana-Rial, Maribel
Valverde, Diana
Núñez-Delgado, Manuel
Fernández-Villar, Alberto
author_sort Leiro-Fernandez, Virginia
collection PubMed
description The evaluation of mediastinal lymph nodes is critical for the correct staging of patients with lung cancer (LC). Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique for mediastinal staging, though unfortunately lymph node micrometastasis is often missed by cytological analysis. The aim of this study was to evaluate the predictive capacity of methylation biomarkers and provide a classification rule for predicting malignancy in false negative EBUS-TBNA samples. The study included 112 patients with a new or suspected diagnosis of LC that were referred to EBUS-TBNA. Methylation of p16/INK4a, MGMT, SHOX2, E-cadherin, DLEC1, and RASSF1A was quantified by nested methylation-specific qPCR in 218 EBUS-TBNA lymph node samples. Cross-validated linear regression models were evaluated to predict malignancy. According to EBUS-TBNA and final diagnosis, 90 samples were true positives for malignancy, 110 were true negatives, and 18 were false negatives. MGMT, SHOX2, and E-cadherin were the methylation markers that better predicted malignancy. The model including sex, age, short axis diameter and standard uptake value of adenopathy, and SHOX2 showed 82.7% cross-validated sensitivity and 82.4% specificity for the detection of malignant lymphadenopathies among negative cytology samples. Our results suggest that the predictive model approach proposed can complement EBUS-TBNA for mediastinal staging.
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spelling pubmed-68263582019-11-18 Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer Leiro-Fernandez, Virginia De Chiara, Loretta Rodríguez-Girondo, Mar Botana-Rial, Maribel Valverde, Diana Núñez-Delgado, Manuel Fernández-Villar, Alberto Cancers (Basel) Article The evaluation of mediastinal lymph nodes is critical for the correct staging of patients with lung cancer (LC). Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique for mediastinal staging, though unfortunately lymph node micrometastasis is often missed by cytological analysis. The aim of this study was to evaluate the predictive capacity of methylation biomarkers and provide a classification rule for predicting malignancy in false negative EBUS-TBNA samples. The study included 112 patients with a new or suspected diagnosis of LC that were referred to EBUS-TBNA. Methylation of p16/INK4a, MGMT, SHOX2, E-cadherin, DLEC1, and RASSF1A was quantified by nested methylation-specific qPCR in 218 EBUS-TBNA lymph node samples. Cross-validated linear regression models were evaluated to predict malignancy. According to EBUS-TBNA and final diagnosis, 90 samples were true positives for malignancy, 110 were true negatives, and 18 were false negatives. MGMT, SHOX2, and E-cadherin were the methylation markers that better predicted malignancy. The model including sex, age, short axis diameter and standard uptake value of adenopathy, and SHOX2 showed 82.7% cross-validated sensitivity and 82.4% specificity for the detection of malignant lymphadenopathies among negative cytology samples. Our results suggest that the predictive model approach proposed can complement EBUS-TBNA for mediastinal staging. MDPI 2019-09-20 /pmc/articles/PMC6826358/ /pubmed/31547177 http://dx.doi.org/10.3390/cancers11101408 Text en © 2019 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
Leiro-Fernandez, Virginia
De Chiara, Loretta
Rodríguez-Girondo, Mar
Botana-Rial, Maribel
Valverde, Diana
Núñez-Delgado, Manuel
Fernández-Villar, Alberto
Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer
title Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer
title_full Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer
title_fullStr Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer
title_full_unstemmed Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer
title_short Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer
title_sort methylation assessment for the prediction of malignancy in mediastinal adenopathies obtained by endobronchial ultrasound-guided transbronchial needle aspiration in patients with lung cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826358/
https://www.ncbi.nlm.nih.gov/pubmed/31547177
http://dx.doi.org/10.3390/cancers11101408
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