Microsatellite Instability, Epstein-Barr Virus, p53, and β-Catenin in Early Gastric Cancers: Clinicopathologic Association

Endoscopic submucosal dissection (ESD) effectively treats selected early gastric cancers (EGCs). However, the association of microsatellite instability (MSI), Epstein-Barr virus (EBV), p53, and β-catenin status with clinicopathologic parameters in EGCs treated with ESD have not been well studied.

We retrospectively collected 312 consecutive EGC cases treated with ESD from January 2021 to December 2023 at Kyungpook National University Chilgok Hospital. MSI polymerase chain reaction, EBV encoded RNA in situ hybridization, and p53 and β-catenin immunostaining were performed for all cases.

Among 312 EGC cases, there were 42 MSI-High (MSI-H) cases (13.5%), 13 EBV-associated gastric cancer (EBVaGC) cases (4.2%), 249 intestinal type cases (79.8%), and eight poorly cohesive carcinoma cases (2.6%). MSI-H was significantly associated with lymphovascular invasion (p=0.02), local recurrence (p=0.03), and synchronous tumors (p<0.001). More than half of EBVaGC cases showed submucosal invasion (61.5%, 8/13) (p=0.016). Consequently, non-curative ESD was more frequently found in EBVaGC than in other subtypes (p<0.001). Mutant p53 patterns and nuclear translocation of β-catenin were almost exclusively found in the intestinal type (p<0.001), without association with clinicopathologic parameters. Margin involvement was frequent in poorly cohesive carcinoma (p=0.003).

We demonstrated that MSI-H and EBVaGC are strongly associated with clinicopathologic parameters and risk factors in EGCs treated with ESD. Molecular testing of gastric cancers should be considered before ESD for better patient management.