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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8303574 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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