Epstein-Barr Virus-Associated Gastric Cancer: A Histopathologic Study With Comprehensive Molecular Profiling

Area of Science:

• Oncology
• Virology
• Genomics

Background:

• Epstein-Barr virus (EBV) is linked to a subset of gastric cancers (GCs).
• Understanding EBV-associated GCs (EBVaGCs) is crucial for targeted therapies.

Purpose of the Study:

• To characterize the histopathological and molecular features of EBVaGCs.
• To identify predictive biomarkers and analyze genomic/transcriptomic profiles.

Main Methods:

• In-situ hybridization for EBV confirmation.
• Immunohistochemistry for HER2, PD-L1, CLDN18, and MMR proteins.
• Next-generation sequencing (AmoyDX Master panel) for genomic and transcriptomic analysis.

Main Results:

• Carcinoma with lymphoid stroma (CLS) was the predominant histotype (69%).
• All EBVaGCs expressed high PD-L1 (CPS ≥10); 66% showed CLDN18 expression.
• PIK3CA (41%) and ARID1A (17%) were frequently altered genes; immune-related gene expression was upregulated.

Conclusions:

• EBVaGC represents a distinct molecular class with unique genomic and immune profiles.
• CLS is a distinct subgroup within EBVaGC, showing pronounced immune activation.
• EBV plays a role in early gastric tumor development.