Mutation analysis of APC gene in gastric cancer with microsatellite instability.

Abstract

To evaluate the role of APC mutation in gastric carcinogenesis and to correlate APC mutation with microsatellite instability (MSI) in gastric carcinomas. APC mutation was measured with multiplex PCR, denaturing gradient gel electrophoresis and DNA sequencing; and MSI was analyzed by PCR-based methods. Sixty-eight cases of sporadic gastric carcinoma were studied for APC mutation at exon 15 and MSI. APC mutations were detected in 15(22.1 %) gastric cancers. Frequence of APC mutation (33.3 %) in intestinal type of gastric cancer was significantly higher than that in diffuse type (13.1 %, P<0.05). On the contrary, no association was observed between APC mutation and tumor size, differentiation, depth of invasion, metastasis or clinical stages. Using five microsatellite markers, MSI in at least one locus was detected in 17 of 68 (25 %) of the tumors analyzed. APC mutations were all detected in MSI-L (only one locus, n=9) or MSS(tumor lacking MSI or stable, n=51), but no mutation was found in MSI-H (> or =2 loci, n=8). APC mutation is involved in carcinogenesis of intestinal type of gastric cancer and is independent of MSI phenotype but related to the LOH pathway in gastric cancer.