Microsatellite instability at multiple loci in gastric carcinoma: clinicopathologic implications and prognosis

Abstract

Background & aims: Microsatellite instability (replication error [RER]-positive phenotype) is a frequent genetic alteration in gastric carcinomas. The clinical relationship between RER-positive and RER-negative gastric tumors is poorly characterized. The aim of this study was to investigate the relationship between the number of altered microsatellite loci and the clinicopathologic features of gastric carcinoma.

Methods: Five or 6 microsatellite loci were analyzed in 61 gastric carcinomas using polymerase chain reaction.

Results: Twenty-one carcinomas (34.4%) had microsatellite instability: 7 at 1 locus, 2 at 2 loci, and 12 at multiple loci. The comparison between the three groups (with none, 1 or 2, and more than 2 RER-positive loci) showed that RER-negative carcinomas and carcinomas with 1 or 2 RER-positive loci share features that differ from those of carcinomas with multiple RER-positive loci. The latter were all of the intestinal or atypical subtype and had lower DNA content, more prominent lymphoid infiltration, and less prevalent nodal metastases than carcinomas in the other two groups. The patients with carcinomas showing multiple RER-positive loci had a better prognosis.

Conclusions: The finding of microsatellite instability in a single or few loci does not qualify a case as a mutator phenotype from a clinical standpoint. Gastric tumors with multiple RER-positive loci have a particular clinicopathologic profile leading to a better outcome.