Aberrant DNA methylation has been shown to play important roles during 
multistage carcinogenesis in various human organs. The aim of this study was to 
evaluate the significance of DNA methyltransferase 1 (DNMT1) protein expression 
during cervical carcinogenesis. We carried out an immunohistochemical 
examination for DNMT1 in 34 samples of histologically normal squamous 
epithelium, 36 samples of low-grade cervical intraepithelial neoplasia (CIN), 61 
samples of higher-grade CIN and 30 samples of squamous cell carcinoma of the 
uterine cervix. The DNMT1 protein expression score, reflecting the intensity and 
incidence of DNMT1 nuclear immunoreactivity, was increased even in low-grade CIN 
(P<0.0001) in comparison with histologically normal squamous epithelium and was 
further increased in higher-grade CIN (P<0.0001 compared to low-grade CIN). The 
DNMT1 protein expression score remained at a plateau in microinvasive carcinoma 
(Stage IA, P=0.0690 compared to higher-grade CIN) and then decreased with cancer 
invasion (Stage IB or more, P=0.0176 compared to Stage IA), whereas the 
proliferating cell nuclear antigen (PCNA) labeling index did not decrease with 
cancer invasion (P=0.8259 between Stage IA and Stage IB or more). Thus, the 
DNMT1 protein expression score and the PCNA labeling index were not mutually 
correlated in squamous cell carcinoma of the uterine cervix (P=0.2304). These 
data suggest that progressively increasing expression of DNMT1 protein is not 
entirely a secondary result of increased cell proliferative activity, but is 
associated with an early step of multistage cervical carcinogenesis.