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

Sep 24, 2026

Gastric cancers are strongly linked to Helicobacter pylori infection, yet only a subset of intestinal metaplasia progresses to carcinogenesis. Short telomere lesions (STLs) were identified in gastrectomy specimens, outside malignant areas, showing localized telomere loss. Histology indicated STLs correspond to intestinal metaplasia with nuclear enlargement but without structural atypia, termed dysplastic metaplasia (DM). Review of 587 H. pylori-positive patients found DM in 32 cases, with high-grade DM showing telomere volume reduction below 60%, increased stemness, TERT expression, and progression to gastric cancer after follow-up.

LanguageEnglish

CategoryHealthcare

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Pages16

Reading Time40 min

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Abstract

Introduction

Background: H. pylori and gastric cancer risk

Telomere shortening and TERT as early events

Rationale: identifying true precancerous lesions

Article Short Telomere Lesions with Dysplastic Metaplasia Histology May Represent Precancerous Lesions of Helicobacter pylori-Positive Gastric Mucosa Rina Fujiwara-Tani 1,*, Tadataka Takagi 1, Shiori Mori 1, Shingo Kishi 1, Yukiko Nishiguchi 1, Takamitsu Sasaki 1, Masayuki Ikeda 2, Kenta Nagai 2, Ujjal Kumar Bhawal 3,4, Hitoshi Ohmori 1, Kiyomu Fujii 1 and Hiroki Kuniyasu 1, * Citation: Fujiwara-Tani, R.; Takagi, T.; Mori, S.; Kishi, S.; Nishiguchi, Y.; Sasaki, T.; Ikeda, M.; Nagai, K.; Bhawal, U.K.; Ohmori, H.; et al. Short Telomere Lesions with Dysplastic Metaplasia Histology May Represent Precancerous Lesions of Helicobacter pylori-Positive Gastric Mucosa. Int. J. Mol. Sci. 2023, 24, 3182. [https://](https://)[ ](https://)[doi.org/10.3390/ijms24043182](doi.org/10.3390/ijms24043182) Academic Editor: Valli De Re Received: 14 November 2022 Revised: 29 January 2023 Accepted: 1 February 2023 Published: 6 February 2023 Copyright: © 2023 by the authors. 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://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Japan 2 Miyoshi Central Hospital, 10531 Higashi-Sakaya-cho, Miyoshi 728-8502, Japan 3 Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo, Matsudo 271-8587, Japan 4 Department of Pharmacology, Saveetha Institute of Medical and Technical Sciences, Saveetha Dental College, Chennai 600077, India * Correspondence: [rina_fuji@naramed-u.ac.jp](rina_fuji@naramed-u.ac.jp) (R.F.-T.); [cooninh@zb4.so-net.ne.jp](cooninh@zb4.so-net.ne.jp) (H.K.); Tel.: +81-744-22-3051 (R.F.-T. & H.K.); Fax: +81-744-25-7308 (R.F.-T. & H.K.) Abstract: 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. Keywords: gastric cancer; precancerous lesion; H. pylori; stemness; telomere 1. Introduction Gastric cancer accounts for approximately 6% of all cancers worldwide and is the ﬁfth most commonly diagnosed malignancy, as well as being the third leading cause of cancerrelated death [1] . Ninety percent of noncardia gastric cancers are associated with

FAQs

What are short telomere lesions (STLs) and how were they identified?

STLs were defined by localized telomere loss outside cancerous lesions in gastrectomy specimens using fluorescence in situ hybridization (FISH).

How does dysplastic metaplasia (DM) relate to intestinal metaplasia?

DM is characterized histologically by intestinal metaplasia with nuclear enlargement but lacking structural atypia, matching the STLs pattern.

What features distinguish high-grade DM and what is its clinical significance?

High-grade DM shows telomere volume reduced to less than 60%, increased stemness, and TERT expression, and more than half progressed to gastric cancer over a 10-year follow-up.

Sep 24, 2026

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