Gastric cancers with microsatellite instability sharing clinical features, chemoresistance and germline MSH6 variants

Recent studies suggest that colorectal cancer with microsatellite instability (MSI) might be resistant to fluorouracil-based chemotherapy; however, little is known about the clinical significance of MSI analysis for gastric cancer. We therefore conducted a prospective single center study analyzing MSI in gastric cancer. Of 123 consecutive gastric cancers analyzed, 12 (9.8 %) were MSI-positive and two patients with MSI-positive gastric cancer underwent systemic chemotherapy because of unresectable disease. Neither cases had concurrent nor past history of other malignancies but one had cancer family history meeting the revised Bethesda criteria. These two MSI-positive gastric cancers shared multiple clinical features, such as direct invasion to adjacent organs, extensive nodal metastasis but no distant metastasis, resistance to fluorouracil and death of tumor bleeding. The two cases had unmethylated MLH1 promoter, suggestive of Lynch syndrome. Germline mutation analysis demonstrated MSH6 alterations of unknown significance in both cases.