Abstract

BackgroundThe clinical role of deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) in gastric cancer (GC) is still controversial. We aimed to analyze the relationship between dMMR/MSI-H and clinicopathological features along with survival.MethodsPatients who were diagnosed with GC at the three big cancer centers in China from 2015 to 2020 were evaluated retrospectively. MMR/MSI status was assessed using immunohistochemistry/PCR. Clinical and pathological data were collected from the medical record system.ResultsA total of 196 patients with dMMR/MSI-H status were enrolled for analysis. The prevalence of MSI-H/dMMR in GC was 6.6%. Another 694 proficient MMR (pMMR) GC patients were enrolled for comparison. Compared with pMMR patients, dMMR/MSI-H patients were associated with older age, female predominance, distal location in the stomach, earlier TNM stage, intestinal subtype, better differentiation, and more negative HER2 status. The median overall survival (OS) of the dMMR/MSI-H group was better than that of the pMMR/microsatellite stability (MSS) group (not reached vs. 53.9 months, p = 0.014). Adjuvant chemotherapy had no impact in both disease-free survival (DFS) and OS of dMMR/MSI-H patients (p = 0.135 and 0.818, respectively). dMMR/MSI-H patients had poorer response and progression-free survival (PFS) of first-line chemotherapy, though they were statistically significant (p = 0.361 and 0.124, respectively).ConclusionsdMMR/MSI-H GC patients have specific clinicopathological characteristics and better prognosis than pMMR patients.

Highlights

  • Gastric cancer (GC) is one of the most common causes of cancerrelated mortality worldwide

  • The prevalence of microsatellite instability (MSI)-H/deficiency of MMR protein function (dMMR) in GC was 6.6%. Another 694 proficient mismatch repair (MMR) GC patients were enrolled for comparison

  • Compared with proficient MMR (pMMR) patients, dMMR/MSI-H patients were associated with older age, female predominance, distal location in the stomach, earlier TNM stage, intestinal subtype, better differentiation, and more negative HER2 status

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Summary

Introduction

Gastric cancer (GC) is one of the most common causes of cancerrelated mortality worldwide. The Cancer Genome Atlas (TCGA) Research Network has identified four distinct molecular subtypes of GC through molecular evaluation of 295 GC patients: EpsteinBarr virus (EBV) positive, microsatellite instability (MSI), chromosomal instability (CIN), and genomically stable (GS) [1]. As a result of dysfunction of mismatch repair (MMR), MSI leads to increased rate of replication error and hypermutational status, which results in increased probability of mutations in oncogenes or tumor suppressors. The concordance between MSI-high (MSI-H) status and deficiency of MMR protein function (dMMR) was 97.6%–99% [2, 3]. The clinical role of deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) in gastric cancer (GC) is still controversial. We aimed to analyze the relationship between dMMR/MSI-H and clinicopathological features along with survival

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