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

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.