title: Cytoplasmic expression of E-cadherin and beta-Catenin correlated with LOH and hypermethylation of the APC gene in oral squamous cell carcinomas.
abstract: BACKGROUND
  Inactivation of the adenomatous polyposis coli (APC) gene results in accumulation and translocation of beta-Catenin, which are important for malignant development. The aim of the present study is to investigate the possible role of APC/beta-Catenin pathway in oral squamous cell carcinomas.
  
  
  METHODS
  The DNA from 34 patients was examined for loss of heterozygosity (LOH) at two markers surrounding the APC, and for hypermethylation of the APC promoter by using methylation-specific polymerase chain reaction (MS-PCR). Fifteen of 34 samples were stained immunohistochemically to show the expression of E-cadherin and beta-Catenin.
  
  
  RESULTS
  We found that cytoplasmic rather than membrane staining of E-cadherin and beta-Catenin was a prominent aberrant tumour-related alteration, and that this expression was mainly present in moderately and poorly differentiated tumours. LOH and hypermethylation of the APC promoter was found in four of 31 and five of 34 carcinoma samples, respectively. Four of five cases presenting LOH/hypermethylation showed cytoplasmic expression of E-cadherin and beta-Catenin by immunohistochemical (IHC) staining.
  
  
  CONCLUSIONS
  The present results indicate that LOH at the APC locus or hypermethylation of the APC promoter 1a may lead to free beta-Catenin accumulation in cytoplasm of oral carcinoma cells and thereby to oral malignant progression.
authors.affiliation: School of Dentistry, University of Copenhagen, Copenhagen, Denmark. shg@mb.au.dk
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.forename: Hans
authors.initials: H
authors.lastname: Eiberg
authors.forename: Annelise
authors.initials: A
authors.lastname: Krogdahl
authors.forename: Chung-Ji
authors.initials: CJ
authors.lastname: Liu
authors.forename: Jens Ahm
authors.initials: JA
authors.lastname: Sørensen
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D019175:DNA Methylation; D017491:Genes, APC; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity / Q000235:genetics*; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin