Correlation of microsatellite instability at multiple loci with long-term survival in advanced gastric carcinoma.

HYPOTHESIS Microsatellite instability (MSI) correlates with clinicopathologic characteristics and long-term prognosis in patients having gastric carcinoma. DESIGN Analysis of prospectively collected data and biologic material. SETTING Tertiary University Hospital, Policlinico "Le Scotte," Siena, Italy. PATIENTS Two hundred fifty patients with gastric carcinoma. MAIN OUTCOME MEASURES Five mononucleotide repeats (BAT-26, BAT-25, NR-24, NR-21, and NR-27) were analyzed in these patients. RESULTS An MSI phenotype was identified in 63 patients (25.2%) and correlated with specific clinicopathologic characteristics. Favorable prognosis was confirmed for patients with an MSI phenotype in univariate (P < .001) and multivariate (P = .05) analyses. Significant differences in clinicopathologic characteristics and long-term prognoses were observed among patients with microsatellite-stable tumors, tumors having instability at 2 to 4 markers, and tumors having instability at all 5 markers (MSI/5). The MSI/5 phenotype was associated with older age (P < .001), female sex (P = .001), antral tumor location (P = .04), intestinal histotype (P = .003), and less infiltration of the serosa (P = .006); lymph node involvement was rare (P < .001) and was limited to few (median, 3) metastatic lymph nodes (P = .001). Long-term survival of patients with the MSI/5 phenotype is favorable and was confirmed in multivariate analysis (relative risk vs patients with stable tumors, 0.32; 95% confidence interval, 0.16-0.63; P = .002). CONCLUSIONS Compared with stable tumors, MSI tumors have distinct clinicopathologic features and are associated with a better prognosis. Patients with the MSI/5 phenotype have a very good prognosis.