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Mismatch-Repair Protein Expression in High-Grade Gliomas: A Large Retrospective Multicenter Study

Background: DNA mismatch repair (MMR) is a system for repairing errors in DNA replication. Cancer cells with MMR deficiency can have immunohistochemical loss of MMR protein expression leading to a hypermutable phenotype that may correlate with anti-PD1 efficacy. Scant data exist about immunohistoche...

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Autores principales: Caccese, Mario, Ius, Tamara, Simonelli, Matteo, Fassan, Matteo, Cesselli, Daniela, Dipasquale, Angelo, Cavallin, Francesco, Padovan, Marta, Salvalaggio, Alessandro, Gardiman, Marina Paola, Skrap, Miran, Zagonel, Vittorina, Lombardi, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555820/
https://www.ncbi.nlm.nih.gov/pubmed/32937743
http://dx.doi.org/10.3390/ijms21186716
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author Caccese, Mario
Ius, Tamara
Simonelli, Matteo
Fassan, Matteo
Cesselli, Daniela
Dipasquale, Angelo
Cavallin, Francesco
Padovan, Marta
Salvalaggio, Alessandro
Gardiman, Marina Paola
Skrap, Miran
Zagonel, Vittorina
Lombardi, Giuseppe
author_facet Caccese, Mario
Ius, Tamara
Simonelli, Matteo
Fassan, Matteo
Cesselli, Daniela
Dipasquale, Angelo
Cavallin, Francesco
Padovan, Marta
Salvalaggio, Alessandro
Gardiman, Marina Paola
Skrap, Miran
Zagonel, Vittorina
Lombardi, Giuseppe
author_sort Caccese, Mario
collection PubMed
description Background: DNA mismatch repair (MMR) is a system for repairing errors in DNA replication. Cancer cells with MMR deficiency can have immunohistochemical loss of MMR protein expression leading to a hypermutable phenotype that may correlate with anti-PD1 efficacy. Scant data exist about immunohistochemical loss of MMR protein expression in high-grade gliomas (HGG). Materials and Methods: We performed a large multicenter retrospective study to investigate the frequency and the prognostic role of immunohistochemical loss of MMR protein expression in HGG patients; we nevertheless evaluated the association between this status and clinical or molecular characteristics. Immunohistochemical loss of MMR protein expression was recorded as partial or complete loss of at least 1 MMR protein. Results: We analyzed the expression of MMR proteins in tumor tissue of 355 consecutive patients. Partial and complete immunohistochemical loss of MMR proteins was found in 43/355 samples (12.1%) and among these, 15 cases (4.2%) showed a complete loss of at the least one MMR protein. Alteration of MSH2 expression was found in 55.8%, MSH6 in 46.5%, PMS2 in 34.9%, and MLH1 in 30.2%. Alteration of MMR protein expression was statistically more frequent in anaplastic gliomas, in recurrent disease, in patients treated with temozolomide, and in IDH-mut gliomas. Immunohistochemical loss of MMR proteins was not associated with survival, adjusting for clinically relevant confounders. Conclusions: MMR protein expression status did not affect survival in HGG patients. We identified clinical and molecular characteristics correlating with immunohistochemical loss of MMR proteins expression. A large study should be performed to analyze its predictive role of immune checkpoint inhibitor efficacy in these subgroups of patients.
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spelling pubmed-75558202020-10-19 Mismatch-Repair Protein Expression in High-Grade Gliomas: A Large Retrospective Multicenter Study Caccese, Mario Ius, Tamara Simonelli, Matteo Fassan, Matteo Cesselli, Daniela Dipasquale, Angelo Cavallin, Francesco Padovan, Marta Salvalaggio, Alessandro Gardiman, Marina Paola Skrap, Miran Zagonel, Vittorina Lombardi, Giuseppe Int J Mol Sci Article Background: DNA mismatch repair (MMR) is a system for repairing errors in DNA replication. Cancer cells with MMR deficiency can have immunohistochemical loss of MMR protein expression leading to a hypermutable phenotype that may correlate with anti-PD1 efficacy. Scant data exist about immunohistochemical loss of MMR protein expression in high-grade gliomas (HGG). Materials and Methods: We performed a large multicenter retrospective study to investigate the frequency and the prognostic role of immunohistochemical loss of MMR protein expression in HGG patients; we nevertheless evaluated the association between this status and clinical or molecular characteristics. Immunohistochemical loss of MMR protein expression was recorded as partial or complete loss of at least 1 MMR protein. Results: We analyzed the expression of MMR proteins in tumor tissue of 355 consecutive patients. Partial and complete immunohistochemical loss of MMR proteins was found in 43/355 samples (12.1%) and among these, 15 cases (4.2%) showed a complete loss of at the least one MMR protein. Alteration of MSH2 expression was found in 55.8%, MSH6 in 46.5%, PMS2 in 34.9%, and MLH1 in 30.2%. Alteration of MMR protein expression was statistically more frequent in anaplastic gliomas, in recurrent disease, in patients treated with temozolomide, and in IDH-mut gliomas. Immunohistochemical loss of MMR proteins was not associated with survival, adjusting for clinically relevant confounders. Conclusions: MMR protein expression status did not affect survival in HGG patients. We identified clinical and molecular characteristics correlating with immunohistochemical loss of MMR proteins expression. A large study should be performed to analyze its predictive role of immune checkpoint inhibitor efficacy in these subgroups of patients. MDPI 2020-09-14 /pmc/articles/PMC7555820/ /pubmed/32937743 http://dx.doi.org/10.3390/ijms21186716 Text en © 2020 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
Caccese, Mario
Ius, Tamara
Simonelli, Matteo
Fassan, Matteo
Cesselli, Daniela
Dipasquale, Angelo
Cavallin, Francesco
Padovan, Marta
Salvalaggio, Alessandro
Gardiman, Marina Paola
Skrap, Miran
Zagonel, Vittorina
Lombardi, Giuseppe
Mismatch-Repair Protein Expression in High-Grade Gliomas: A Large Retrospective Multicenter Study
title Mismatch-Repair Protein Expression in High-Grade Gliomas: A Large Retrospective Multicenter Study
title_full Mismatch-Repair Protein Expression in High-Grade Gliomas: A Large Retrospective Multicenter Study
title_fullStr Mismatch-Repair Protein Expression in High-Grade Gliomas: A Large Retrospective Multicenter Study
title_full_unstemmed Mismatch-Repair Protein Expression in High-Grade Gliomas: A Large Retrospective Multicenter Study
title_short Mismatch-Repair Protein Expression in High-Grade Gliomas: A Large Retrospective Multicenter Study
title_sort mismatch-repair protein expression in high-grade gliomas: a large retrospective multicenter study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555820/
https://www.ncbi.nlm.nih.gov/pubmed/32937743
http://dx.doi.org/10.3390/ijms21186716
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