In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 11 ( 2021-11-11), p. e0258878-
Abstract:
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. Methods 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, p16 INK2 , and p21 Cip1 ; 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. Results 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. Conclusions Our findings demonstrate different patterns of regulatory protein expression in adenomas than serrated lesions, especially involving apoptosis. ClinicalTrials.gov Identifier: NCT00272324
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0258878
DOI:
10.1371/journal.pone.0258878.g001
DOI:
10.1371/journal.pone.0258878.t001
DOI:
10.1371/journal.pone.0258878.t002
DOI:
10.1371/journal.pone.0258878.t003
DOI:
10.1371/journal.pone.0258878.t004
DOI:
10.1371/journal.pone.0258878.t005
DOI:
10.1371/journal.pone.0258878.s001
DOI:
10.1371/journal.pone.0258878.s002
DOI:
10.1371/journal.pone.0258878.s003
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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