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

Recent molecular studies have suggested that hyperplastic duct lesions of the pancreas are potential precursors of pancreatic ductal carcinoma. This study examines the type, distribution, age-related incidence and K-ras codon 12 mutation rate of duct lesions in the normal pancreas. Postmortem pancreases from 140 patients were screened for the presence of mucinous cell hypertrophy (MHT), ductal papillary hyperplasia (DPH), adenomatoid ductal hyperplasia (ADH), and squamous metaplasia (SQM). Microdissected cell samples were analyzed for K-ras codon 12 mutations by polymerase chain reaction amplification of exon 1 of the K-ras gene, combined with constant denaturing gel electrophoresis, and analyzed by sequencing. Of the 140 specimens 114 showed duct lesions. The lesions were evenly distributed throughout the pancreas. 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 duct lesions and a variant of ADH with dense stroma. 67% of the K-ras-positive specimens showed the transition GGT to GAT (8) or GTT (5). Hyperplastic/metaplastic duct changes of the pancreas increase with age, but their distribution pattern in the pancreas differs from that of ductal carcinomas.