Duct changes and K-ras mutations in the disease-free pancreas: analysis oftype, age relation and spatial distribution

Recent molecular studies have suggested that hyperplastic duct lesions of t he pancreas are potential precursors of pancreatic ductal carcinoma. This s tudy examines the type, distribution, age-related incidence and K-ras codon 12 mutation rate of duct lesions in the normal pancreas. Postmortem pancre ases from 140 patients were screened for the presence of mucinous cell hype rtrophy (MHT), ductal papillary hyperplasia (DPH), adenomatoid ductal hyper plasia (ADH), and squamous metaplasia (SQM). Microdissected cell samples we re analyzed for K-ras codon 12 mutations by polymerase chain reaction ampli fication of exon 1 of the K-ras gene, combined with constant denaturing gel electrophoresis, and analyzed by sequencing. Of the 140 specimens 114 show ed duct lesions. The lesions were evenly distributed throughout the pancrea s. They were more common beyond the age of 40. MHT was present in 68%, DPH in 36%, ADH in 40%, and SQM in 36% of the cases. K-ras mutations were found in 19 samples from 15 out of 79 pancreases (18%), including all types of d uct lesions and a variant of ADH with dense stroma. 67% of the K-ras-positi ve specimens showed the transition GGT to GAT (8) or GTT (5). Hyperplastic/ metaplastic duct changes of the pancreas increase with age, but their distr ibution pattern in the pancreas differs from that of ductal carcinomas.