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

Abstract

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