Microsatellite instability, prognosis and metastasis in gastric cancers from a low-risk population

We examined 169 cases of gastric adenocarcinoma for microsatellite instabil ity (MSI), using a panel of 8 microsatellite markers. Of these Eases, 142 w ere from the United States, a country of relatively low risk for gastric ca ncer. Comparing microdissected tumors to normal cells from the same patient , we classified tumors as being microsatellite-stable (MSS) or having a low frequency of MSI (MSI-L, up to 30% of markers different in the tumor) or a high frequency of MSI (MSI-H, 30% or more of markers different). Among our American cases, we identified 26(18.2%) showing MSI-H and 15 (10.6%) showi ng MSI-L, Twenty cases were from Korean patients, and they showed no signif icant differences in proportions of MSI-H and MSI-L from the American cases . MSI-H tumors in the American patients were characterized by elevated freq uencies of band shifts in repeat sequences of the BAX (50%), transforming g rowth factor-beta receptor type II (TCF beta RII, 68.9%), beta(2)-microglob ulin (21.4%) and E2F4 (51.7%) genes. Alterations in E2F4 in MSI-H tumors we re always integral multiples of 3 nucleotides lost or gained, which would n ot cause a frameshift mutation, and within the range of normal polymorphism s for this sequence. North American patients (n = 127) with MSI-H and MSI-L tumors had a longer median survival of 541 days and 587 days, respectively , compared to 265 days for patients with MSS tumors (p = 0.027), This survi val difference may result from a significantly greater tendency for metasta ses in the MSS group (p = 0.031). (C) 2000 Wiley-Liss, Inc.