Carcinogenesis in the Remnant Stomach Following Distal Gastrectomy with Billroth II Reconstruction is Associated with High-level Microsatellite Instability

Abstract

Although the gastric remnant has been reported to be at high risk for carcinogenesis, the process of carcinogenesis of gastric remnant cancer (GRC) remains unclear. In this study, genetic alterations in GRC were examined in order to investigate the carcinogenic pathways of GRC. Twenty-one patients with GRC were investigated and were compared to 36 patients with sporadic gastric cancer (GC) as a control group. Microsatellite instability (MSI) was examined using 8 primer marker sets. Immunohistochemical staining for hMLH1 and hMSH2 as the DNA mismatch repair system was performed. The high-level MSI (MSI-H) frequency (43%; 9/21) of GRC was significantly higher (p=0.001) than that of the sporadic GC (6%; 2/36). The MSI-H incidence (67%: 8/12) of GRC after gastrojejunostomy (Billroth II anastomosis) was significantly (p=0.015) higher than that (11%: 1/9) after gastroduodenostomy (Billroth I anastomosis). The MSI-H in GRC was significantly (p<0.0001) associated with lack of expression of both hMLH1 and hMSH2. The inactivation of hMLH1 or hMSH2 was significantly frequent (p=0.035) in GRC after gastrojejunostomy (58%: 7/12), compared with that in gastroduodenostomy (11%: 1/9). GRC was more closely associated with the MSI pathway than sporadic GC. Carcinogenesis in the remnant stomach following distal gastrectomy with gastrojejunostomy was found to be associated with the MSI pathway due to inactivation of the DNA mismatch repair system.