title: Immunohistochemical expression of DNA methyltransferases 1, 3a, and 3b in actinic cheilitis and lip squamous cell carcinomas.
abstract: BACKGROUND
  Epigenetic modifications, including DNA methylation of tumor suppressor genes carried out by DNA methyltransferases (DNMTs), are important events in carcinogenesis. Although there are studies concerning to its expression in several cancer types, DNMTs expression pattern is not known in photoinduced lip carcinogenesis. The aim of this study was to investigate the immunoexpression of DNMTs 1, 3a, and 3b in lip precancerous lesion (actinic cheilitis) and cancer.
  
  
  METHODS
  Thirty cases of actinic cheilitis (AC), thirty cases of lip squamous cell carcinoma (LSCC), and twenty cases of non-neoplastic tissue (NNT) were selected for immunohistochemical investigation of DNMTs 1, 3a, and 3b.
  
  
  RESULTS
  Nuclear DNMT 1 immunoreactivity was significantly higher in the LSCC group (68.6%) compared with NNT (47%), and nuclear DNMT 3b was higher in LSCC (70.9%) than in NNT (37.9%) and in AC (44%). Only DNMT 3a showed both higher nuclear and cytoplasmic expression in AC (35.9% and 35.5%, respectively) than in NNT (4.4% and 16.1%, respectively) and LSCC (8.8% and 13.2%, respectively) (P < 0.05).
  
  
  CONCLUSIONS
  The results suggested that DNMT 3a could play a key role in the methylation process of initial steps of UV carcinogenesis present in AC while DNMT 3b could be responsible for de novo methylation in already established lip cancer.
authors.affiliation: Pathology Department and Dentistry Graduate Program, Federal University of Santa Catarina, Florianopolis, Santa Catarina, Brazil. filipe.daniel@ufsc.br.
authors.forename: Filipe I
authors.initials: FI
authors.lastname: Daniel
authors.affiliation: Private Dentist, Florianopolis, Santa Catarina, Brazil.
authors.forename: Soraia R
authors.initials: SR
authors.lastname: Alves
authors.affiliation: Pathology Department, Federal University of Santa Catarina, Florianopolis, Santa Catarina, Brazil.
authors.forename: Daniella S C
authors.initials: DS
authors.lastname: Vieira
authors.affiliation: Morphology Sciences Department and Dentistry Graduate Program, Federal University of Santa Catarina, Florianopolis, Santa Catarina, Brazil.
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Biz
authors.affiliation: Pediatrics Department, Federal University of Santa Catarina, Florianopolis, Santa Catarina, Brazil.
authors.forename: Inah W B S
authors.initials: IW
authors.lastname: Daniel
authors.affiliation: Pathology Department and Dentistry Graduate Program, Federal University of Santa Catarina, Florianopolis, Santa Catarina, Brazil.
authors.forename: Filipe
authors.identifier: http://orcid.org/0000-0002-5395-0486
authors.initials: F
authors.lastname: Modolo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D063646:Carcinogenesis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D002613:Cheilitis / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000096:biosynthesis* / Q000378:metabolism; D000090205:DNA Methyltransferase 3A; D005260:Female; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008048:Lip Neoplasms / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D055815:Young Adult; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D012097:Repressor Proteins; D000097584:DNA Methyltransferase 3B; C411744:DMAP1 protein, human; C000717967:DNMT3A protein, human
keywords: DNA methylation; actinic cheilitis; lip cancer; methyltransferases; squamous cell carcinoma