Disparate cell proliferation and p53 overexpression in colonic crypts with normal epithelial lining found below the neoplastic canopy of conventional adenomas

Abstract We previously found colonic crypts with normal epithelial lining but with corrupted shapes (NECS) beneath the adenomatous tissue of conventional adenomas (CoAs). Here we assessed the distribution of proliferating cells (PCs) and explored the possible occurrence of p53‐upregulated cells in t...

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Main Authors: Carlos A Rubio, Peter T Schmidt
Format: Article
Language:English
Published: Wiley 2019-07-01
Series:The Journal of Pathology: Clinical Research
Subjects:
Online Access:https://doi.org/10.1002/cjp2.128
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author Carlos A Rubio
Peter T Schmidt
author_facet Carlos A Rubio
Peter T Schmidt
author_sort Carlos A Rubio
collection DOAJ
description Abstract We previously found colonic crypts with normal epithelial lining but with corrupted shapes (NECS) beneath the adenomatous tissue of conventional adenomas (CoAs). Here we assessed the distribution of proliferating cells (PCs) and explored the possible occurrence of p53‐upregulated cells in the NECS in a cohort of CoAs. Sections from 70 CoAs and from 12 normal colon segments were immunostained with the proliferation marker Ki67. In 60 of the 70 CoAs, additional sections were immunostained for the tumor suppressor p53 protein. NECS with asymmetric, haphazardly distributed single PC or PC clusters were recorded in 80% of the CoAs, with a continuous PC domain in one or both slopes of the crypts in 17%, and with haphazardly distributed single PCs in the remaining 3% of the CoAs. In the 12 normal segments (controls), the colon crypts demonstrated normal shapes with symmetric PC domains limited to the lower third portion of the crypts. In 30% of the 60 CoAs immunostained with p53 the NECS revealed haphazardly distributed p53‐upregulated cells, singly or in clusters. In sum, the apparently normal epithelium of the NECS beneath the adenomatous tissue of CoAs revealed an unprecedented relocation of the normal PC domains. This unexpected event and the occurrence of p53‐upregulated cells strongly suggest that the crypts beneath the neoplastic tissue of CoAs harbor somatic mutations. The accretion of putative mutated NECS beneath the neoplastic canopy of CoA emerges as a previously unaddressed major event, an event that might play an important role in the histogenesis of CoA in the human colon.
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spelling doaj.art-d8a024e29ec74be482468244db04da9a2022-12-21T22:38:21ZengWileyThe Journal of Pathology: Clinical Research2056-45382019-07-015315416310.1002/cjp2.128Disparate cell proliferation and p53 overexpression in colonic crypts with normal epithelial lining found below the neoplastic canopy of conventional adenomasCarlos A Rubio0Peter T Schmidt1Department of Pathology Karolinska Institute and University Hospital Stockholm SwedenDepartment of Medicine Karolinska Institute and University Hospital, Centre for Digestive Diseases Stockholm SwedenAbstract We previously found colonic crypts with normal epithelial lining but with corrupted shapes (NECS) beneath the adenomatous tissue of conventional adenomas (CoAs). Here we assessed the distribution of proliferating cells (PCs) and explored the possible occurrence of p53‐upregulated cells in the NECS in a cohort of CoAs. Sections from 70 CoAs and from 12 normal colon segments were immunostained with the proliferation marker Ki67. In 60 of the 70 CoAs, additional sections were immunostained for the tumor suppressor p53 protein. NECS with asymmetric, haphazardly distributed single PC or PC clusters were recorded in 80% of the CoAs, with a continuous PC domain in one or both slopes of the crypts in 17%, and with haphazardly distributed single PCs in the remaining 3% of the CoAs. In the 12 normal segments (controls), the colon crypts demonstrated normal shapes with symmetric PC domains limited to the lower third portion of the crypts. In 30% of the 60 CoAs immunostained with p53 the NECS revealed haphazardly distributed p53‐upregulated cells, singly or in clusters. In sum, the apparently normal epithelium of the NECS beneath the adenomatous tissue of CoAs revealed an unprecedented relocation of the normal PC domains. This unexpected event and the occurrence of p53‐upregulated cells strongly suggest that the crypts beneath the neoplastic tissue of CoAs harbor somatic mutations. The accretion of putative mutated NECS beneath the neoplastic canopy of CoA emerges as a previously unaddressed major event, an event that might play an important role in the histogenesis of CoA in the human colon.https://doi.org/10.1002/cjp2.128conventional colon adenomasnormal cryptscorrupted shapesabnormal cell proliferation
spellingShingle Carlos A Rubio
Peter T Schmidt
Disparate cell proliferation and p53 overexpression in colonic crypts with normal epithelial lining found below the neoplastic canopy of conventional adenomas
The Journal of Pathology: Clinical Research
conventional colon adenomas
normal crypts
corrupted shapes
abnormal cell proliferation
title Disparate cell proliferation and p53 overexpression in colonic crypts with normal epithelial lining found below the neoplastic canopy of conventional adenomas
title_full Disparate cell proliferation and p53 overexpression in colonic crypts with normal epithelial lining found below the neoplastic canopy of conventional adenomas
title_fullStr Disparate cell proliferation and p53 overexpression in colonic crypts with normal epithelial lining found below the neoplastic canopy of conventional adenomas
title_full_unstemmed Disparate cell proliferation and p53 overexpression in colonic crypts with normal epithelial lining found below the neoplastic canopy of conventional adenomas
title_short Disparate cell proliferation and p53 overexpression in colonic crypts with normal epithelial lining found below the neoplastic canopy of conventional adenomas
title_sort disparate cell proliferation and p53 overexpression in colonic crypts with normal epithelial lining found below the neoplastic canopy of conventional adenomas
topic conventional colon adenomas
normal crypts
corrupted shapes
abnormal cell proliferation
url https://doi.org/10.1002/cjp2.128
work_keys_str_mv AT carlosarubio disparatecellproliferationandp53overexpressionincoloniccryptswithnormalepithelialliningfoundbelowtheneoplasticcanopyofconventionaladenomas
AT petertschmidt disparatecellproliferationandp53overexpressionincoloniccryptswithnormalepithelialliningfoundbelowtheneoplasticcanopyofconventionaladenomas