Microsatellite instability is a genetic marker for the development of multiple gastric cancers

Multiple gastric cancers are found in 5-15% of all patients with gastric ca ncer. However, no molecular markers have yet been shown to be clinically us eful for predicting which patient will or will not have multiple gastric ca ncers. Recently, microsatellite instability (MSI) has been identified as a molecular marker for multiple colorectal cancers. To elucidate whether MSI could be used as a molecular marker for multiple gastric cancers, we examin ed MSI in 38 patients with a single gastric cancer, in 26 patients with syn chronous multiple gastric cancers and in 14 patients with metachronous mult iple gastric cancers. In the patients with synchronous multiple gastric can cers, 1 of the larger tumors was examined. In the patients with metachronou s multiple gastric cancers, the first gastric cancer was examined. Five mic rosatellite loci, Including D17S855, D18S58, D18S61, BAT25 and BAT40, were examined with microsatellite assay. MSI was divided into low frequency of M SI (MSI-L) and high frequency of MSI (MSI-H) by the number of affected loci . MSI-L was detected in 3 of the 38 (8%) patients with a single gastric can cer, in 7 of the 26 (27%) patients with synchronous multiple gastric cancer s and in 6 of the 14 (43%) patients with metachronous multiple gastric canc ers. MSI-H was detected only in I of the 38 (3%) patients with a single gas tric cancer. The frequency of MSI-L was significantly higher in patients wi th multiple gastric cancers, both synchronous and metachronous, than in tho se with a single gastric cancer, (p < 0.05 and p < 0.01, respectively). Pat ients with MSI(+) gastric cancer developed a significantly higher frequency of secondary gastric cancer, when compared with patients with MSI(-) gastr ic cancer (p < 0.05). These data suggest that MSI may play an important rol e in the development of multiple gastric cancers, and it may be used clinic ally as a molecular marker for the prediction of multiple gastric cancers. (C) 2001 Wiley-Liss, Inc.