Molecular comparison of gastric cancer specimens from Japan with those of Americans of European descent

Major differences exist between the epidemiology of gastric cancer in Japan and the United States. Most importantly, the 7-year survival following curative gastrectomy is markedly different in the West than in the East. While a higher proportion of gastric cancers in Japan are localized (node negative) cancers, the stage-stratified survival after gastrectomy for gastric cancer is superior in Japan compared to the West. These differences likely reflect unique gene-environment interactions on gastric carcinogenesis. The process of carcinogenesis may differ in gastric cancers from Japan and America and account for prognostic differences, as patients of Asian descent treated in America also exhibit superior survival. Molecular differences in gastric cancer from the two regions, however, have not been intensively investigated. This body of work examined paraffin embedded formalin fixed tissue blocks from Japanese patients and American patients of European descent who had undergone gastrectomy for gastric cancer not involving the gastro-esophageal junction. E-cadherin, a favorable prognostic biomarker, was expressed on significantly more malignant cells from Japanese cancers with intestinal histology (48.4% versus 17.5%, p = 0.03). E-cadherin expression on diffuse cancers from the two regions was similar (34.4% among Japanese versus 41.5% among American). Among 16 American and Japanese specimens matched for age, gender, histology and stage, E-cadherin was expressed on a higher proportion of malignant cells from Japanese specimens (49.9% versus 22.2%, p = 0.11) and c-erbB2 was expressed on a higher proportion of malignant cells from American specimens (30% versus 14%, p = 0.10). The frequency of microsatellite instability (MSI) in Japanese gastric carcinoma specimens was higher than in specimens from American patients of European descent (39% versus 20%). Specimens demonstrating MSI were more likely to be of advanced stage (T2 or T3) among Japanese patients (86%) and of early stage (T1) among American patients (75%; p = 0.021).; Our results provide a molecular explanation for the superior survival of Japanese gastric cancer patients. If the biology of gastric cancer in the Far East in less aggressive than that in the United States, it is likely that the treatments will need to be individualized.