Mutation analysis of APC gene in gastric cancer with microsatellite instability

AIM:To evaluate the role of APC mutation in gastriccarcinogenesis and to correlate APC mutation withmicrosatellite instability(MSI)in gastric carcinomas.METHODS:APC mutation was measured with multiplexPCR,denaturing gradient gel electrophoresis and DNAsequencing;and MSI was analyzed by PCR-based methods.RESULTS:Sixty-eight cases of sporadic gastric carcinomawere studied for APC mutation at exon 15 and MSI.APCmutaions were detected in 15(22.1%)gastric cancers.Frequence of APC mutation(33.3 %)in intestinal type ofgastric cancer was significantly higher than that in diffusetype(13.1%,P<0.05).On the contrary,no association wasobserved between APC mutation and tumor size,differentiation,depth of invasion,metastasis or clinical stages.Using five microsatellite markers,MSI in at least one locuswas 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 nomutation was found in MSI-H(≥2 loci,n=-8).CONCLUSION:APC mutation is involved in carcinogenesisof intestinal type of gastric cancer and is independent of MSIphenotype but related to the LOH pathway in gastric cancer.