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 epithe...

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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
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:8cbe8a4e2e0142cbbbdc9f2c2b443dbc2021-12-02T20:07:38ZProliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions.1932-620310.1371/journal.pone.0258878https://doaj.org/article/8cbe8a4e2e0142cbbbdc9f2c2b443dbc2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258878https://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: NCT00272324.Jane 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, p e0258878 (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/8cbe8a4e2e0142cbbbdc9f2c2b443dbc
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