Proliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions

<h4>Background</h4> Adenomas and serrated lesions represent heterogeneous sets of early precursors in the colorectum with varying malignant potential. They are often distinguished by their histopathologic differences, but little is known about potential differences in regulation of epith...

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Autores principales:	Jane C. Figueiredo, Michael N. Passarelli, Wei Wei, Dennis J. Ahnen, Jeffrey S. Morris, Lynda Corley, Trupti Mehta, Angela N. Bartley, Gail McKeown-Eyssen, Robert S. Bresalier, Elizabeth L. Barry, Ajay Goel, Goretti Hernandez Mesa, Stanley R. Hamilton, John A. Baron
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3a9ccd59033c4cde9ecdae9e99397cde
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spelling	oai:doaj.org-article:3a9ccd59033c4cde9ecdae9e99397cde2021-11-18T08:14:35ZProliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions1932-6203https://doaj.org/article/3a9ccd59033c4cde9ecdae9e99397cde2021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584700/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4> Adenomas and serrated lesions represent heterogeneous sets of early precursors in the colorectum with varying malignant potential. They are often distinguished by their histopathologic differences, but little is known about potential differences in regulation of epithelial proliferation and apoptosis. <h4>Methods</h4> We conducted a protein expression analysis using tissue microarrays of 625 colorectal adenomas and 142 serrated lesions to determine potential differences in regulation of epithelial proliferation and apoptosis. We quantitated proliferation with Ki-67; apoptosis with activated caspase-3 (CASP3); up- and down-regulators of proliferation with cyclin D1, p16INK2, and p21Cip1; and apoptosis regulators with BAX, BCL2, and survivin. Linear mixed effects models and circos diagrams were used to determine relationships among expression and lesion characteristics. <h4>Results</h4> Adenomas had a significantly higher CASP-3 labeling index (LI) than serrated lesions, resulting in a lower net growth ratio (Ki-67 LI/activated CASP-3 LI, p-value<0.0001). Cyclin D1 LI, p16 LI and p21 LI were lower in adenomas compared to serrated lesions, while expression of both BCL2 and BAX were higher (p <0.001). Among adenomas, cyclin D1 LI and p16 LI levels increased with greater villous component, and the highest BAX expression was detected in adenomas larger than 2 cm (both p<0.0001). Right-sided adenomas had higher CASP3 LI than left colorectal adenomas (p = 0.008). Significant differences in cyclin D1 LI, p21 LI and survivin LI were also observed across histopathologic subtypes of serrated lesions. <h4>Conclusions</h4> Our findings demonstrate different patterns of regulatory protein expression in adenomas than serrated lesions, especially involving apoptosis. ClinicalTrials.gov Identifier:NCT00272324Jane C. FigueiredoMichael N. PassarelliWei WeiDennis J. AhnenJeffrey S. MorrisLynda CorleyTrupti MehtaAngela N. BartleyGail McKeown-EyssenRobert S. BresalierElizabeth L. BarryAjay GoelGoretti Hernandez MesaStanley R. HamiltonJohn A. BaronPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jane C. Figueiredo Michael N. Passarelli Wei Wei Dennis J. Ahnen Jeffrey S. Morris Lynda Corley Trupti Mehta Angela N. Bartley Gail McKeown-Eyssen Robert S. Bresalier Elizabeth L. Barry Ajay Goel Goretti Hernandez Mesa Stanley R. Hamilton John A. Baron Proliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions
description	<h4>Background</h4> Adenomas and serrated lesions represent heterogeneous sets of early precursors in the colorectum with varying malignant potential. They are often distinguished by their histopathologic differences, but little is known about potential differences in regulation of epithelial proliferation and apoptosis. <h4>Methods</h4> We conducted a protein expression analysis using tissue microarrays of 625 colorectal adenomas and 142 serrated lesions to determine potential differences in regulation of epithelial proliferation and apoptosis. We quantitated proliferation with Ki-67; apoptosis with activated caspase-3 (CASP3); up- and down-regulators of proliferation with cyclin D1, p16INK2, and p21Cip1; and apoptosis regulators with BAX, BCL2, and survivin. Linear mixed effects models and circos diagrams were used to determine relationships among expression and lesion characteristics. <h4>Results</h4> Adenomas had a significantly higher CASP-3 labeling index (LI) than serrated lesions, resulting in a lower net growth ratio (Ki-67 LI/activated CASP-3 LI, p-value<0.0001). Cyclin D1 LI, p16 LI and p21 LI were lower in adenomas compared to serrated lesions, while expression of both BCL2 and BAX were higher (p <0.001). Among adenomas, cyclin D1 LI and p16 LI levels increased with greater villous component, and the highest BAX expression was detected in adenomas larger than 2 cm (both p<0.0001). Right-sided adenomas had higher CASP3 LI than left colorectal adenomas (p = 0.008). Significant differences in cyclin D1 LI, p21 LI and survivin LI were also observed across histopathologic subtypes of serrated lesions. <h4>Conclusions</h4> Our findings demonstrate different patterns of regulatory protein expression in adenomas than serrated lesions, especially involving apoptosis. ClinicalTrials.gov Identifier:NCT00272324
format	article
author	Jane C. Figueiredo Michael N. Passarelli Wei Wei Dennis J. Ahnen Jeffrey S. Morris Lynda Corley Trupti Mehta Angela N. Bartley Gail McKeown-Eyssen Robert S. Bresalier Elizabeth L. Barry Ajay Goel Goretti Hernandez Mesa Stanley R. Hamilton John A. Baron
author_facet	Jane C. Figueiredo Michael N. Passarelli Wei Wei Dennis J. Ahnen Jeffrey S. Morris Lynda Corley Trupti Mehta Angela N. Bartley Gail McKeown-Eyssen Robert S. Bresalier Elizabeth L. Barry Ajay Goel Goretti Hernandez Mesa Stanley R. Hamilton John A. Baron
author_sort	Jane C. Figueiredo
title	Proliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions
title_short	Proliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions
title_full	Proliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions
title_fullStr	Proliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions
title_full_unstemmed	Proliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions
title_sort	proliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/3a9ccd59033c4cde9ecdae9e99397cde
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Proliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions

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