Clinicopathological features and immune checkpoint expression patterns in dMMR early gastric cancer - a retrospective pilot study

Sep 22, 2026

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Mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) status is used to predict immune checkpoint inhibitor (ICI) effectiveness, yet treatment outcomes remain inadequate. This retrospective pilot study examines clinical characteristics of dMMR/MSI-H early gastric cancer and evaluates how immune checkpoint molecules are expressed within the tumor microenvironment. Twenty early gastric cancer cases (Nov 2019–Jul 2024) were analyzed by immunohistochemistry, with deeper immune-checkpoint profiling in dMMR cases.

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CategoryResearch & Report

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Abstract

Background

Method

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Introduction

Yokotani et al. BMC Cancer (2026) 26:1008 BMC Cancer [https://doi.org/10.1186/s12885-026-16298-3](https://doi.org/10.1186/s12885-026-16298-3) RESEARCH Open Access Clinicopathological features and immune checkpoint expression patterns in dMMR early gastric cancer: a retrospective pilot study Yusaku Yokotani1*, Naoyuki Sakamoto1, Mikiko Matsuo2, Yuki Nakahata 1, Haruka Okuyama1, Rieko Mukai1, Junji Nagano 1, Akihiro Obora1, Yoshiki Murakami1, Takao Kojima1 and Nobuaki Yagi1 Abstract Background Although mismatch repair–deficient (dMMR)/microsatellite and instability–high (MSI-H) status is recognized as a biomarker that predicts the efficiency of immune checkpoint inhibitors (ICIs), the efficacy of ICIs treatment is still insufficient. Accordingly, insights into the mechanisms of acquired resistance to ICIs in gastrointestinal cancers are necessary, and developing immunotherapeutic strategies to improve response rates is an urgent clinical priority. We investigated the clinical characteristics of dMMR/MSI-H early gastric cancer and analyzed the expression patterns of immune checkpoint molecules within the tumor microenvironment. Method A total of 20 cases of early gastric cancer, treated between November 2019 and July 2024, were included. Immunohistochemistry was performed to assess the expression of mismatch repair (MMR) protein, and patient clinical characteristics were evaluated. Additionally, among the eight cases identified as dMMR early gastric cancer, they were further examined for the expression of immune checkpoint molecules in the tumor microenvironment using immunohistochemical staining. Result The median age of patients diagnosed with dMMR early gastric cancer was 73 years. In 20 patients, female sex and severe atrophy were associated with dMMR status in univariate analysis (OR 7. 67, 95% CI 1.04–94. 53) . The expression pattern of immune checkpoint molecules showed heterogeneity. Conclusion These findings highlight the heterogeneity of immune checkpoint expression patterns and provide preliminary, hypothesis-generating insights into variability in response to PD-1/PD-L1 blockade. keywords dMMR, Early gastric cancer, Immune checkpoint, PD-L1, LAG-3, TIM-3, Tumor microenvironment *Correspondence: Yusaku Yokotani yokotani01 [15@gmail.com](15@gmail.com) 1Department of Gastroenterology, Asahi University Hospital, Gifu, Japan 2Department of Pathology, Asahi University Hospital, Gifu, Japan © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/.)[.](http://creativecommons.org/licenses/by/4.0/.) Yokotani et al. BMC Cancer (2026) 26:1008 Introduction Importantly, mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) status has emerged asa predictive biomarker for immune checkpoint inhibitor (ICI) therapy across solid tumors, including gastric cancer (GC). Additionally, the identification of molecular subtypes, particularly MSI-H or dMMR tumors, has provided new insights into the biology of several types of cancer. Current guidelines, therefore, recommend routine MSI/MMR testing to individualize treatment and highlight the po

FAQs

What problem does the study address about ICI therapy in dMMR/MSI-H early gastric cancer?

Even though dMMR/MSI-H status is a recognized biomarker for ICI efficiency, overall efficacy is still insufficient, and mechanisms of acquired resistance require clarification.

How were the 20 early gastric cancer cases selected and evaluated?

The study included 20 cases treated from November 2019 to July 2024. Immunohistochemistry was used to assess mismatch repair (MMR) protein and clinical characteristics, followed by immune-checkpoint staining in dMMR early gastric cancer cases.

What were the key findings regarding immune checkpoint expression?

Patients with dMMR early gastric cancer had a median age of 73 years, and immune checkpoint molecule expression showed heterogeneity, suggesting variability in response to PD-1/PD-L1 blockade.

Sep 22, 2026

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