Aberrant DNA methylation has been shown to play an important role during 
multistage carcinogenesis in various human organs. The aim of the present study 
was to evaluate the significance of DNA methyltransferase 1 (DNMT1) protein 
expression during pancreatic carcinogenesis. Immunohistochemical analysis of 
DNMT1 in 48 peripheral pancreatic duct epithelia showing no remarkable 
histological findings without an inflammatory background (DE), 54 peripheral 
pancreatic duct epithelia with an inflammatory background (DEI), 188 pancreatic 
intraepithelial neoplasias (PanIN), and 220 areas of invasive ductal carcinoma 
from surgical specimens resected from 100 patients, was carried out. The average 
incidence of DNMT1 immunoreactivity increased progressively from DE to DEI (P = 
0.003), from DE and DEI to PanIN (P < 0.0001), among PanIN with different grades 
of dysplasia (from PanIN I to PanIN II, P = 0.0012), from PanIN to invasive 
ductal carcinomas (P < 0.0001) and among invasive ductal carcinomas with 
different grades of histological differentiation (from well or moderately to 
poorly differentiated adenocarcinomas, P < 0.0001). High-level DNMT1 protein 
expression in invasive ductal carcinomas was correlated significantly with an 
advanced t category (P = 0.0224) and an advanced stage (P = 0.0294). Moreover, 
patients with invasive ductal carcinomas showing high-level DNMT1 protein 
expression had a poorer outcome (P = 0.0469). These data suggest that increased 
DNMT1 protein expression participates in multistage pancreatic carcinogenesis 
from the precancerous stage to malignant progression of ductal carcinomas and 
may be a biological predictor of poor prognosis.