Microsatellite instable early gastric cancers; a distinct molecular profile with HER2 over-expression and increased multiple lesion risk

BACKGROUND/AIMS: Microsatellite instability (MSI) associated gastric cancers (GCs) have a large burden of mutational risk. In advanced gastric cancers (AGCs), the pre-treatment evaluation of MSI and over-expression of HER2 / EGFR could be crucial for prognosis. However, the significance of MSI state, HER2, and EGFR over-expression in early gastric cancer (EGC) are still under investigation. METHOD: A consecutive study was undertaken from March 2020 to March 2022, and we analyzed 325 gastric cancer tissues (165 EGCs; 160 AGCs) from the patients who had received gastrectomy or endoscopic submucosal dissection. RESULTS: The frequencies of MSI and HER2 over-expression were 21.8% (71/ 325), and 14.5% (47/ 325), respectively. The frequency of EGFR over-expression was 48.9% (159/ 325). The infection rate of Helicobacter pylori was 50.8% (165/325), and the infection rate in EGC (58.8%, 97/165) was significantly higher than that in AGC (42.5%, 68/160) (P < 0.01). EGFR overexpression was more frequent in AGC than in EGC (P = 0.03), and there was no statistical difference for MSI and HER2. In MSI positive GCs, HER2 over-expression (P = 0.03) and H. pylori infection (P = 0.03) were more frequent than in microsatellite stable GCs. HER2 over-expression was outstanding in MSI EGCs (P < 0.01), and multiple lesions were observed more clinically. CONCLUSION: The frequency of H. pylori infection and HER2 over-expression occurred more frequently in MSI positive GCs. In particular, HER2 overexpression was more evident in MSI-EGC. MSI-EGC is a group of diseases with unique molecular biological characteristics and may show rapid tumor growth potential, so special treatment measures may be needed.