ANALYSIS OF K-RAS ONCOGENE MUTATIONS IN CHRONIC-PANCREATITIS WITH DUCTAL HYPERPLASIA

Background. K-ras oncogene mutations have been identified in up to 95% of pancreatic cancers, implying their critical role in their molecula r pathogenesis. However, the earliest stage in which K-ras mutations c an be detected in potential precursor lesions of pancreatic cancer rem ains unclear. This study evaluates pancreatic ductal hyperplasia in th e setting of chronic pancreatitis, which predisposes to pancreatic can cer development, for K-ras codon 12 and 13 mutations. Methods. Paraffi n-embedded surgical specimens from 42 patients with chronic pancreatit is were examined microscopically for the presence of ductal hyperplasi a. Both hyperplastic and nonhyperplastic ducts were microdissected fro m the specimens that contained hyperplasia (11 of 42). Four of the rem aining specimens without hyperplasia served as controls. Genomic DNA w as extracted, and polymerase chain reaction and amplification of the K -ras oncogene was performed. Polymerase chain reaction products were e valuated by means of hybridization to mutant specific oligonucleotide probes and by means of automated DNA sequencing.Results. K-ras codon 1 2 mutations representative glycine to valine substitutions were presen t in 2 of (18%) 11 patients with ductal hyperplasia. No mutations were found in the controls without ductal hyperplasia. Conclusions. Our st udy supports the premise that K-ras mutations develop in a subset of c hronic pancreatitis associated hyperplasia and provides a genetic basi s for the potential progression of chronic pancreatitis to pancreatic cancer.