MICROSATELLITE INSTABILITY AND LOSS OF HETEROZYGOSITY IN GASTRIC-CARCINOMA IN COMPARISON TO FAMILY HISTORY

We compared 29 gastric carcinomas from patients with a variably strong family history for gastric cancer (group 1) with 36 gastric carcinoma s from patients without a family history of this disease (group 2) for microsatellite instability (MSI) and loss of heterozygosity (LOH) wit h 12 microsatellite markers, Both study groups had similar proportions of histological types and tumor locations, Widespread MSI (alteration s at greater than or equal to 6 loci) was seen in 5 of 29 (17%) of the tumors belonging to group 1 and in 4 of 36 (11%) group 2 tumors, MSI at a low level (alterations at 1 to 3 loci) was observed in 12 of 29 ( 41%) of tumors in group 1 and in 10 of 36 (28%) of tumors in group 2, differences that were not statistically significant. A significant dif ference with respect to low level MSI was observed between the two gro ups when considering the overall mutation rate of microsatellites, Sev enteen of 281 (6%) analyzed microsatellite loci showed alterations in group 1 and 11 of 381 (2.9%) in group 2 (P = 0.046). Comparison of bot h types of MSI to the clinicopathological parameters in both groups re vealed a significant association of low level MSI with advanced tumor stages (P = 0.046) in the group 2, whereas no such association was obs erved in group 1, In respect to LOH, a significant difference between the two groups was observed at chromosome 17p12, as 13 of 22 (59%) inf ormative cases of group 1 showed LOH in comparison with 7 of 26 (27%) (P = 0.024) in group 2. No correlation of LOH at chromosome 17p12 to t he pathological or clinical data was observed either in the two groups or in the study as a whole. Our data show that gastric carcinomas of patients with a positive family history of gastric cancer in group 1 a re characterized by a higher mutation rate in respect to low level MSI , particularly at dinucleotide repeats, and by a higher frequency of L OH at chromosome 17p12, indicating that different genetic pathways are involved in the pathogenesis of gastric carcinomas arising in patient s with and without a familial background of this disease.