Microsatellite instability in Japanese vs European American patients with gastric cancer.

Background: The stage-stratified survival following gastrectomy for gastric cancer is far better in Japan than in the United States. The process of carcinogenesis may differ in gastric cancers from Japan and the United States, accounting for prognostic differences, as patients of Asian descent treated in United States also exhibit superior survival in comparison with non-Asian patients.

Hypothesis: The phenotype of gastric cancer differs between Japanese and American patients.

Design: Retrospective case-case (blinded) study.

Setting: University hospitals in Japan and the United States.

Patients And Methods: We compared the frequency of microsatellite instability (MSI) at 7 loci from formalin-fixed paraffin-embedded gastrectomy specimens, between cases of gastric cancer at Hitachi General Hospital (N = 18) and in US patients of European descent treated in Orange County, Calif (N = 20). Microsatellite instability, Lauren classification, and T stage were determined without knowledge of the country of origin of the specimens.

Main Outcome Measure: The frequency of MSI in Japanese vs European American gastric cancer specimens.

Results: The frequency of MSI in Japanese gastric carcinoma specimens was higher than in specimens from American patients of European descent (39% vs 20%, respectively). In contrast, a high frequency of MSI was demonstrated in only 3 European American specimens (15% of all specimens in this group). Tumors from Japanese and American men were more likely to demonstrate MSI than those from women (50% vs 5.6%, respectively; P =.004). Among advanced-stage tumors, Japanese specimens were significantly more likely to demonstrate MSI (55%) than European American specimens (7.1%; P =.02). Specimens from Japan and America demonstrating MSI were equally likely to be from men, involve the gastroesophageal junction, and demonstrate intestinal histologic abnormalities.

Conclusions: Advanced gastric cancers from Japan are more likely to demonstrate MSI. These data warrant a study of larger numbers of patients to assess whether differences in MSI expression correlates with prognostic differences between gastric carcinoma in patients in Japan vs the United States.