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MSI Analysis in Solid and Liquid Biopsies of Gastroesophageal Adenocarcinoma Patients: A Molecular Approach

Gastroesophageal adenocarcinoma (GEA) patients with the microsatellite instability (MSI) subtype emerged as optimal candidates for immunotherapy. To date, immunohistochemistry (IHC) is the gold standard for MSI assessment in formalin-fixed paraffin-embedded (FFPE) specimens. However, IHC, although u...

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Autores principales: Boldrin, Elisa, Piano, Maria Assunta, Alfieri, Rita, Mazza, Marcodomenico, Vassallo, Loretta, Scapinello, Antonio, Pilati, Pierluigi, Curtarello, Matteo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303574/
https://www.ncbi.nlm.nih.gov/pubmed/34298864
http://dx.doi.org/10.3390/ijms22147244
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author Boldrin, Elisa
Piano, Maria Assunta
Alfieri, Rita
Mazza, Marcodomenico
Vassallo, Loretta
Scapinello, Antonio
Pilati, Pierluigi
Curtarello, Matteo
author_facet Boldrin, Elisa
Piano, Maria Assunta
Alfieri, Rita
Mazza, Marcodomenico
Vassallo, Loretta
Scapinello, Antonio
Pilati, Pierluigi
Curtarello, Matteo
author_sort Boldrin, Elisa
collection PubMed
description Gastroesophageal adenocarcinoma (GEA) patients with the microsatellite instability (MSI) subtype emerged as optimal candidates for immunotherapy. To date, immunohistochemistry (IHC) is the gold standard for MSI assessment in formalin-fixed paraffin-embedded (FFPE) specimens. However, IHC, although useful for diagnostic typing, cannot be used to analyze cell-free DNA (cfDNA) in liquid biopsy, a tool that could overcome tumor heterogeneity and enable longitudinal monitoring. In order to find an alternative diagnostic method to IHC, we analyzed 86 retrospective GEAs FFPE samples with multiplex PCR. Moreover, to verify the feasibility of MSI detection in liquid biopsy, cfDNA samples of five patients that resulted in having MSI in a prospective cohort of 35 patients were evaluated by multiplex PCR, real-time PCR and droplet digital PCR (ddPCR). Analysis of FFPE showed 100% concordance between multiplex PCR and IHC (Cohen’s Kappa agreement = 1). On the contrary, only ddPCR was able to detect MSI in cfDNAs of T3/T4 GEA patients. In conclusion, data highlight the molecular analysis as an optimal alternative to IHC for the diagnostic typing and suggest that the ddPCR assay can be considered as the most reliable and promising molecular approach to detect MSI in the cfDNA of GEA patients.
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spelling pubmed-83035742021-07-25 MSI Analysis in Solid and Liquid Biopsies of Gastroesophageal Adenocarcinoma Patients: A Molecular Approach Boldrin, Elisa Piano, Maria Assunta Alfieri, Rita Mazza, Marcodomenico Vassallo, Loretta Scapinello, Antonio Pilati, Pierluigi Curtarello, Matteo Int J Mol Sci Article Gastroesophageal adenocarcinoma (GEA) patients with the microsatellite instability (MSI) subtype emerged as optimal candidates for immunotherapy. To date, immunohistochemistry (IHC) is the gold standard for MSI assessment in formalin-fixed paraffin-embedded (FFPE) specimens. However, IHC, although useful for diagnostic typing, cannot be used to analyze cell-free DNA (cfDNA) in liquid biopsy, a tool that could overcome tumor heterogeneity and enable longitudinal monitoring. In order to find an alternative diagnostic method to IHC, we analyzed 86 retrospective GEAs FFPE samples with multiplex PCR. Moreover, to verify the feasibility of MSI detection in liquid biopsy, cfDNA samples of five patients that resulted in having MSI in a prospective cohort of 35 patients were evaluated by multiplex PCR, real-time PCR and droplet digital PCR (ddPCR). Analysis of FFPE showed 100% concordance between multiplex PCR and IHC (Cohen’s Kappa agreement = 1). On the contrary, only ddPCR was able to detect MSI in cfDNAs of T3/T4 GEA patients. In conclusion, data highlight the molecular analysis as an optimal alternative to IHC for the diagnostic typing and suggest that the ddPCR assay can be considered as the most reliable and promising molecular approach to detect MSI in the cfDNA of GEA patients. MDPI 2021-07-06 /pmc/articles/PMC8303574/ /pubmed/34298864 http://dx.doi.org/10.3390/ijms22147244 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Boldrin, Elisa
Piano, Maria Assunta
Alfieri, Rita
Mazza, Marcodomenico
Vassallo, Loretta
Scapinello, Antonio
Pilati, Pierluigi
Curtarello, Matteo
MSI Analysis in Solid and Liquid Biopsies of Gastroesophageal Adenocarcinoma Patients: A Molecular Approach
title MSI Analysis in Solid and Liquid Biopsies of Gastroesophageal Adenocarcinoma Patients: A Molecular Approach
title_full MSI Analysis in Solid and Liquid Biopsies of Gastroesophageal Adenocarcinoma Patients: A Molecular Approach
title_fullStr MSI Analysis in Solid and Liquid Biopsies of Gastroesophageal Adenocarcinoma Patients: A Molecular Approach
title_full_unstemmed MSI Analysis in Solid and Liquid Biopsies of Gastroesophageal Adenocarcinoma Patients: A Molecular Approach
title_short MSI Analysis in Solid and Liquid Biopsies of Gastroesophageal Adenocarcinoma Patients: A Molecular Approach
title_sort msi analysis in solid and liquid biopsies of gastroesophageal adenocarcinoma patients: a molecular approach
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303574/
https://www.ncbi.nlm.nih.gov/pubmed/34298864
http://dx.doi.org/10.3390/ijms22147244
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