Immunohistochemical expression of DNA methyltransferases 1, 3a and 3b in oral leukoplakias and squamous cell carcinomas.
Over-expression of DNA methyltransferases DNMT1, DNMT3a and DNMT3b has been reported in various cancers and precancerous lesions.


OBJECTIVE
To investigate DNMT1, DNMT3a and DNMT3b enzymes in oral squamous cell carcinoma (SCC) and leukoplakia, and their relationship with histopathologic/clinical parameters.


METHODS
Immunohistochemistry was carried out to evaluate the three DNMTs in 60 samples of oral SCC and 37 samples of oral leukoplakia.


RESULTS
DNMT3a immunoreactivity in the three groups of oral SCC (39.8%) was significantly higher than in control (22.6%) (ANOVA, Student-Newman-Keuls test, P<0.05), but not when compared to oral leukoplakia groups (28.2%). For DNMT1 and DNMT3b, there were no statistically significant differences between oral SCC groups (65% and 74.7%), oral leukoplakia groups (68.3% and 70.9%) and control (65.4% and 76.5%). There was a significantly higher mean percentage of DNMT1 immunoreactivity in non-smokers (ANOVA, P=0.048), and a higher DNMT3a immunoreactivity in alcohol users (ANOVA, P=0.01).


CONCLUSIONS
Higher DNMT3a immunopositivity may be associated with oral SCC and alcohol use, whilst lower levels of DNMT1 may be related with smoking habit. However, there was a significantly higher mean percentage of DNMT1 immunoreactivity in non-smokers (ANOVA, P=0.048), and a higher DNMT3a immunoreactivity in alcohol users (ANOVA, P=0.010).
Daniel
Filipe Ivan
FI
School of Dentistry, Oral Medicine Division, Pontifical Catholic University of Rio Grande do Sul, Brazil. fidaniel@brturbo.com.br
Rivero
Elena Riet Correa
ER
Modolo
Filipe
F
Lopes
Tiago Giuliani
TG
Salum
Fernanda Gonçalves
FG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002467:Cell Nucleus / Q000473:pathology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000032:analysis*; D000090205:DNA Methyltransferase 3A; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007972:Leukoplakia, Oral / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000473:pathology*; D011230:Precancerous Conditions / Q000473:pathology; D012907:Smoking; D055815:Young Adult; D000097584:DNA Methyltransferase 3B
D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C000619380:DNMT1 protein, human