Clinicopathological characteristics of Epstein-Barr virus and microsatellite instability subtypes of early gastric neoplasms classified by the Japanese and the World Health Organization criteria

Gastric cancer is a heterogenous disease with different phenotypes, genotypes, and clinical progress. Discrepancies in the histological diagnosis of gastric neoplasms remain problematic, and international harmonization should be performed to improve our understanding of gastric carcinogenesis. Gastric cancer associated with Epstein-Barr virus (EBV) and microsatellite-unstable tumors are considered to be two major subtypes. We re-evaluated Japanese cases of early gastric cancer according to the current World Health Organization (WHO) criteria and classified them into genomic subtypes based on microsatellite instability (MSI) and EBV to determine the initial genetic events in gastric carcinogenesis. A total of 113 Japanese gastric cancers treated with endoscopic resection over 5 years were archived in our hospital. A histological re-evaluation according to the WHO criteria revealed 54 adenocarcinomas, which were divided into 6 EBV-positive (11.1%), 7 MSI-high (13.0%), and 41 microsatellite stable (MSS) cases (75.9%). Histologically, EBV-positive carcinomas were poorly differentiated, and MSI-high cancers were frequent in well to moderately differentiated adenocarcinoma, indicating that EBV-positive subtype presented with a histologically atypical morphology in the early gastric carcinogenesis. Our study indicated that the WHO criteria were useful for subdividing Japanese gastric cancer cases, and this subdivision may be useful for comparative examinations between the precursor and early carcinoma.