ANALYSIS OF K-RAS GENE MUTATION IN HYPERPLASTIC DUCT CELLS OF THE PANCREAS WITHOUT PANCREATIC DISEASE

Background & Aims: We and others have previously shown that the mutati on of K-ras codon 12 was found in the majority of pancreatic adenocarc inomas. The mutation has also been identified in the pancreatic duct w ith mucous cell hyperplasia in association with chronic pancreatitis, Ductal hyperplasia is also frequently found in the pancreas free from pancreatic carcinoma or chronic pancreatitis. The aim of this study wa s to assess the incidence and types of mutations in hyperplastic foci in these cases. Methods:The nucleotide sequence of the K-ras gene at c odon 12 of the DNA extracted from microdissected hyperplastic epitheli um of the pancreatic duct obtained at autopsy in patients without panc reatic adenocarcinoma or chronic pancreatitis was analyzed, Results: O f 38 patients with 79 hyperplastic foci, 12 patients (with 19 hyperpla stic foci) had mutations. None of the 16 normal ducts in 12 specimens had this mutation. The nucleotide sequence of the codon in 53% of duct al hyperplastic foci was TGT or AGT, both of which were not found in 3 0 cases of adenocarcinoma. Conclusions: These results suggest that the res gene mutation occurs frequently in multifocal hyperplastic foci o f pancreatic duct and that the mutations may not have direct relevance to the carcinogenesis of pancreatic cancer.