Open AccessIncreased DNA methyltransferase 1 (DNMT1) protein expression in precancerous conditions and ductal carcinomas of the pancreas
Author(s) -
Peng DunFa,
Kanai Yae,
Sawada Morio,
Ushijima Saori,
Hiraoka Nobuyoshi,
Kosuge Tomoo,
Hirohashi Setsuo
Publication year - 2005
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2005.00071.x
Subject(s) - pancreatic intraepithelial neoplasia , carcinogenesis , pathology , dnmt1 , medicine , methyltransferase , immunohistochemistry , ductal carcinoma , pancreatic duct , pancreas , dysplasia , dna methylation , pancreatic cancer , carcinoma in situ , cancer research , carcinoma , oncology , cancer , biology , methylation , breast cancer , gene expression , pancreatic ductal adenocarcinoma , biochemistry , gene
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. ( Cancer Sci 2005; 96: 403–408)