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Short Telomere Lesions with Dysplastic Metaplasia Histology May Represent Precancerous Lesions of Helicobacter pylori-Positive Gastric Mucosa

Gastric cancers are strongly associated with Helicobacter pylori infection, with intestinal metaplasia characterizing the background mucosa in most cases. However, only a subset of intestinal metaplasia cases proceed to carcinogenesis, and the characteristics of high-risk intestinal metaplasia that...

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Autores principales: Fujiwara-Tani, Rina, Takagi, Tadataka, Mori, Shiori, Kishi, Shingo, Nishiguchi, Yukiko, Sasaki, Takamitsu, Ikeda, Masayuki, Nagai, Kenta, Bhawal, Ujjal Kumar, Ohmori, Hitoshi, Fujii, Kiyomu, Kuniyasu, Hiroki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958872/
https://www.ncbi.nlm.nih.gov/pubmed/36834592
http://dx.doi.org/10.3390/ijms24043182
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author Fujiwara-Tani, Rina
Takagi, Tadataka
Mori, Shiori
Kishi, Shingo
Nishiguchi, Yukiko
Sasaki, Takamitsu
Ikeda, Masayuki
Nagai, Kenta
Bhawal, Ujjal Kumar
Ohmori, Hitoshi
Fujii, Kiyomu
Kuniyasu, Hiroki
author_facet Fujiwara-Tani, Rina
Takagi, Tadataka
Mori, Shiori
Kishi, Shingo
Nishiguchi, Yukiko
Sasaki, Takamitsu
Ikeda, Masayuki
Nagai, Kenta
Bhawal, Ujjal Kumar
Ohmori, Hitoshi
Fujii, Kiyomu
Kuniyasu, Hiroki
author_sort Fujiwara-Tani, Rina
collection PubMed
description Gastric cancers are strongly associated with Helicobacter pylori infection, with intestinal metaplasia characterizing the background mucosa in most cases. However, only a subset of intestinal metaplasia cases proceed to carcinogenesis, and the characteristics of high-risk intestinal metaplasia that link it with gastric cancer are still unclear. We examined telomere reduction in five gastrectomy specimens using fluorescence in situ hybridization, and identified areas with localized telomere loss (outside of cancerous lesions), which were designated as short telomere lesions (STLs). Histological analyses indicated that STLs were characteristic of intestinal metaplasia accompanied by nuclear enlargement but lacking structural atypia, which we termed dysplastic metaplasia (DM). A review of gastric biopsy specimens from 587 H. pylori-positive patients revealed 32 cases of DM, 13 of which were classified as high-grade based on the degree of nuclear enlargement. All high-grade DM cases exhibited a telomere volume reduced to less than 60% of that of lymphocytes, increased stemness, and telomerase reverse transcriptase (TERT) expression. Two patients (15%) exhibited low levels of p53 nuclear retention. After a 10-year follow-up, 7 (54%) of the high-grade DM cases had progressed to gastric cancer. These results suggest that DM is characterized by telomere shortening, TERT expression, and stem cell proliferation, and high-grade DM is a high-grade intestinal metaplasia that likely represents a precancerous lesion of gastric cancer. High-grade DM is expected to effectively prevent progression to gastric cancer in H. pylori-positive patients.
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spelling pubmed-99588722023-02-26 Short Telomere Lesions with Dysplastic Metaplasia Histology May Represent Precancerous Lesions of Helicobacter pylori-Positive Gastric Mucosa Fujiwara-Tani, Rina Takagi, Tadataka Mori, Shiori Kishi, Shingo Nishiguchi, Yukiko Sasaki, Takamitsu Ikeda, Masayuki Nagai, Kenta Bhawal, Ujjal Kumar Ohmori, Hitoshi Fujii, Kiyomu Kuniyasu, Hiroki Int J Mol Sci Article Gastric cancers are strongly associated with Helicobacter pylori infection, with intestinal metaplasia characterizing the background mucosa in most cases. However, only a subset of intestinal metaplasia cases proceed to carcinogenesis, and the characteristics of high-risk intestinal metaplasia that link it with gastric cancer are still unclear. We examined telomere reduction in five gastrectomy specimens using fluorescence in situ hybridization, and identified areas with localized telomere loss (outside of cancerous lesions), which were designated as short telomere lesions (STLs). Histological analyses indicated that STLs were characteristic of intestinal metaplasia accompanied by nuclear enlargement but lacking structural atypia, which we termed dysplastic metaplasia (DM). A review of gastric biopsy specimens from 587 H. pylori-positive patients revealed 32 cases of DM, 13 of which were classified as high-grade based on the degree of nuclear enlargement. All high-grade DM cases exhibited a telomere volume reduced to less than 60% of that of lymphocytes, increased stemness, and telomerase reverse transcriptase (TERT) expression. Two patients (15%) exhibited low levels of p53 nuclear retention. After a 10-year follow-up, 7 (54%) of the high-grade DM cases had progressed to gastric cancer. These results suggest that DM is characterized by telomere shortening, TERT expression, and stem cell proliferation, and high-grade DM is a high-grade intestinal metaplasia that likely represents a precancerous lesion of gastric cancer. High-grade DM is expected to effectively prevent progression to gastric cancer in H. pylori-positive patients. MDPI 2023-02-06 /pmc/articles/PMC9958872/ /pubmed/36834592 http://dx.doi.org/10.3390/ijms24043182 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fujiwara-Tani, Rina
Takagi, Tadataka
Mori, Shiori
Kishi, Shingo
Nishiguchi, Yukiko
Sasaki, Takamitsu
Ikeda, Masayuki
Nagai, Kenta
Bhawal, Ujjal Kumar
Ohmori, Hitoshi
Fujii, Kiyomu
Kuniyasu, Hiroki
Short Telomere Lesions with Dysplastic Metaplasia Histology May Represent Precancerous Lesions of Helicobacter pylori-Positive Gastric Mucosa
title Short Telomere Lesions with Dysplastic Metaplasia Histology May Represent Precancerous Lesions of Helicobacter pylori-Positive Gastric Mucosa
title_full Short Telomere Lesions with Dysplastic Metaplasia Histology May Represent Precancerous Lesions of Helicobacter pylori-Positive Gastric Mucosa
title_fullStr Short Telomere Lesions with Dysplastic Metaplasia Histology May Represent Precancerous Lesions of Helicobacter pylori-Positive Gastric Mucosa
title_full_unstemmed Short Telomere Lesions with Dysplastic Metaplasia Histology May Represent Precancerous Lesions of Helicobacter pylori-Positive Gastric Mucosa
title_short Short Telomere Lesions with Dysplastic Metaplasia Histology May Represent Precancerous Lesions of Helicobacter pylori-Positive Gastric Mucosa
title_sort short telomere lesions with dysplastic metaplasia histology may represent precancerous lesions of helicobacter pylori-positive gastric mucosa
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958872/
https://www.ncbi.nlm.nih.gov/pubmed/36834592
http://dx.doi.org/10.3390/ijms24043182
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