Widespread microsatellite instability occurs infrequently in adenocarcinoma of the gastric cardia

Hereditary non-polyposis colorectal cancer (HNPCC) is associated with an increased predisposition to colorectal cancer and extra-colonic cancers of the gastro-intestinal, urological and female reproductive tracts, These tumours are characterised by an underlying defect in DNA mismatch repair and exhibit numerous replication errors throughout the genome (RER(+) phenotype), HNPCC-associated gastric tumours, and a subset of sporadic, distally-located gastric tumours exhibit this RER(+) phenotype, It is recognised that proximal gastric tumours exhibit distinct epidemiological features, In this study we investigated the occurrence of microsatellite instability in a series of 38 primary gastric adenocarcinomas, arising in the proximal stomach, A total of 138 microsatellite markers, comprising mainly dinucleotide and tetranucleotide repeat units and covering all autosomal arms, excluding acrocentric arms, were analysed, One tumour demonstrated somatic microsatellite alterations at 62% (26 of 42) of loci tested, A further 32 tumours demonstrated levels of microsatellite instability ranging from 0.8% (1 of 128)-11.4% (15 of 132) of loci tested, Five tumours demonstrated no microsatellite alterations at any of the loci tested, These findings suggest that a high percentage of proximal gastric carcinomas exhibit a low level of microsatellite alterations at dinucleotide and tetranucleotide repeat loci, However, ubiquitous somatic alterations at these loci, characteristic of HNPCC-associated tumours, occur in a relatively small proportion of tumours.