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Conventional colon adenomas harbor various disturbances in microsatellite stability and contain micro-serrated foci with microsatellite instability

INTRODUCTION: Colorectal cancer belongs to the most frequent occurring malignancies. A prediction of the clinical outcome and appropriate choice of neoadjuvant chemotherapy needs personalized insight to the main driving pathways. Because most CRCs have polyps as progenitor lesions, studying the path...

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Autores principales: Lewitowicz, Piotr, Gluszek, Stanislaw, Koziel, Dorota, Horecka-Lewitowicz, Agata, Chrapek, Magdalena, Wolak, Przemyslaw, Klusek, Justyna, Nasierowska-Guttmejer, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325232/
https://www.ncbi.nlm.nih.gov/pubmed/28234922
http://dx.doi.org/10.1371/journal.pone.0172381
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author Lewitowicz, Piotr
Gluszek, Stanislaw
Koziel, Dorota
Horecka-Lewitowicz, Agata
Chrapek, Magdalena
Wolak, Przemyslaw
Klusek, Justyna
Nasierowska-Guttmejer, Anna
author_facet Lewitowicz, Piotr
Gluszek, Stanislaw
Koziel, Dorota
Horecka-Lewitowicz, Agata
Chrapek, Magdalena
Wolak, Przemyslaw
Klusek, Justyna
Nasierowska-Guttmejer, Anna
author_sort Lewitowicz, Piotr
collection PubMed
description INTRODUCTION: Colorectal cancer belongs to the most frequent occurring malignancies. A prediction of the clinical outcome and appropriate choice of neoadjuvant chemotherapy needs personalized insight to the main driving pathways. Because most CRCs have polyps as progenitor lesions, studying the pathways driving to adenomagenesis is no less important. GOALS: Our purpose was the evaluation of microsatellite stability status within conventional colon adenomas and also β-catenin, BRAFV600E and p53 contribution. MATERIAL AND METHODS: The cohort included 101 cases of typical colon adenomas with high grade epithelial dysplasia according to WHO. An immunohistochemistry method was used for the depiction of the expression of targeted proteins, as also their heterogeneity. RESULTS: Generally, we noted a 10% frequency of MSI events where MSI-H reached a 5% share occurred within the left colon and rectal polyps. β-catenin nuclear overexpression was noted with a 70% frequency and p53 with close to a 24% frequency. In addition, we found a presence of micro-serration foci more often within tubular adenomas, where focal MSI took place more often. Our results indicate that MSI events occur more often than had been theorized earlier. It results in tumour heterogeneity, more complex underlying pathways and finally ontogenetic molecular-diversity of tumours besides similar occurring histopathological features.
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spelling pubmed-53252322017-03-09 Conventional colon adenomas harbor various disturbances in microsatellite stability and contain micro-serrated foci with microsatellite instability Lewitowicz, Piotr Gluszek, Stanislaw Koziel, Dorota Horecka-Lewitowicz, Agata Chrapek, Magdalena Wolak, Przemyslaw Klusek, Justyna Nasierowska-Guttmejer, Anna PLoS One Research Article INTRODUCTION: Colorectal cancer belongs to the most frequent occurring malignancies. A prediction of the clinical outcome and appropriate choice of neoadjuvant chemotherapy needs personalized insight to the main driving pathways. Because most CRCs have polyps as progenitor lesions, studying the pathways driving to adenomagenesis is no less important. GOALS: Our purpose was the evaluation of microsatellite stability status within conventional colon adenomas and also β-catenin, BRAFV600E and p53 contribution. MATERIAL AND METHODS: The cohort included 101 cases of typical colon adenomas with high grade epithelial dysplasia according to WHO. An immunohistochemistry method was used for the depiction of the expression of targeted proteins, as also their heterogeneity. RESULTS: Generally, we noted a 10% frequency of MSI events where MSI-H reached a 5% share occurred within the left colon and rectal polyps. β-catenin nuclear overexpression was noted with a 70% frequency and p53 with close to a 24% frequency. In addition, we found a presence of micro-serration foci more often within tubular adenomas, where focal MSI took place more often. Our results indicate that MSI events occur more often than had been theorized earlier. It results in tumour heterogeneity, more complex underlying pathways and finally ontogenetic molecular-diversity of tumours besides similar occurring histopathological features. Public Library of Science 2017-02-24 /pmc/articles/PMC5325232/ /pubmed/28234922 http://dx.doi.org/10.1371/journal.pone.0172381 Text en © 2017 Lewitowicz et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lewitowicz, Piotr
Gluszek, Stanislaw
Koziel, Dorota
Horecka-Lewitowicz, Agata
Chrapek, Magdalena
Wolak, Przemyslaw
Klusek, Justyna
Nasierowska-Guttmejer, Anna
Conventional colon adenomas harbor various disturbances in microsatellite stability and contain micro-serrated foci with microsatellite instability
title Conventional colon adenomas harbor various disturbances in microsatellite stability and contain micro-serrated foci with microsatellite instability
title_full Conventional colon adenomas harbor various disturbances in microsatellite stability and contain micro-serrated foci with microsatellite instability
title_fullStr Conventional colon adenomas harbor various disturbances in microsatellite stability and contain micro-serrated foci with microsatellite instability
title_full_unstemmed Conventional colon adenomas harbor various disturbances in microsatellite stability and contain micro-serrated foci with microsatellite instability
title_short Conventional colon adenomas harbor various disturbances in microsatellite stability and contain micro-serrated foci with microsatellite instability
title_sort conventional colon adenomas harbor various disturbances in microsatellite stability and contain micro-serrated foci with microsatellite instability
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325232/
https://www.ncbi.nlm.nih.gov/pubmed/28234922
http://dx.doi.org/10.1371/journal.pone.0172381
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