To examine genetic instability during carcinogenesis, we screened 171 carcinomas of the breast, liver, proximal colon, stomach, pancreas, uterine cervix, and ovary for replication error at four microsatellite marker loci on chromosome 2, 3, and 17. A significantly high incidence of genetic instability was observed in pancreatic (6 of 9 tumors) and gastric cancers (22 of 57 cases). In other types of carcinoma, the incidence of replication error-positive cases was relatively low (3-16%). Among gastric carcinomas, significantly more replication error-positive cases were observed in the poorly differentiated types (16 of 25 cases) than in well differentiated types (3 of 18) (P = 0.0023 by Fisher's exact test). Our results suggested that genetic instability is likely to play an important role in development of pancreatic and gastric cancers, particularly poorly differentiated adenocarcinomas.
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