SPORADIC GASTRIC CARCINOMAS WITH MICROSATELLITE INSTABILITY DISPLAY APARTICULAR CLINICOPATHOLOGICAL PROFILE

Mutations in recently identified genes on chromosomes 2 and 3 seem to be responsible for repair errors (RER(+)) throughout the genome. This novel genetic mechanism was first reported in hereditary non-polyposis colorectal cancer syndrome and in cancers that are characteristic of this syndrome, such as carcinomas of the right colon, stomach and endo metrium. We investigated the frequency of RER(+) phenotype in a series of 34 sporadic gastric carcinomas, in an attempt to see if the RER(+) cases displayed any particular morphologic features and/or if they sh owed distinctive clinicopathologic characteristics. Twelve loci were i nvestigated. We found 23 RER(-) cases (67.6%) and 11 RER(+) cases (32. 4%). A significant association was found between RER(+) carcinomas and localization of the tumors: 9 of the 11 RER(+) carcinomas (81.8%) wer e located at the antrum whereas all the cardiac tumors were RER(-). Th e RER(+) phenotype was also significantly related to the presence of m oderate/abundant T-cell lymphoid infiltration within the tumors. The 3 -year survival rate of patients with RER(+) tumors was suggestively lo nger than that of patients with RER(-) tumors. No significant relation ship was found between several clinicopathologic characteristics of th e cases, including age, sex, staging, histologic type and ploidy, desp ite a trend towards an association between RER(+) phenotype and advanc ed age of the patients and poorly differentiated, intestinal type of t he carcinomas. The high frequency of microsatellite instability in spo radic gastric carcinomas supports the involvement of this genetic mech anism in gastric carcinogenesis. Gastric carcinomas with the RER(+) ph enotype tend to occur as poorly differentiated adenocarcinomas in the antrum of elderly patients, display abundant T-cell infiltration and c arry a relatively good prognosis. (C) 1995 Wiley-Liss, Inc.