title: Molecular alterations of E-cadherin and beta-catenin in brain metastases.
abstract: The molecular mechanisms and candidate genes involved in metastasis to the brain need elucidation. In the present study brain metastases were analyzed regarding changes of E-cadherin (CDH1) and beta-catenin (CTNNB1). Loss of heterozygosity (LOH) of the CDH1 gene was detected in 42.2% of samples. The highest frequency of LOHs was observed in metastases from primary sites of lung adenocarcinoma and small cell lung cancer. Metastases from breast and colon demonstrated changes in 55.6% and 50% of cases. Downregulation of E-cadherin protein was observed in 83% of samples. Only 21.1% of samples with E-cadherin LOH had beta-catenin located in the nucleus. Image analysis showed that the quantities of E-cadherin and beta-catenin were significantly positively correlated (P = 0.008). Changes of E-cadherin were frequent in brain metastases that we investigated. Lack of mutations of beta-catenin, the fact that it was not frequently found in the nucleus and the positive correlation between the two proteins may suggest that the break-up of adherens junctions, and not the activation of wnt signaling, is responsible for metastasis formation.
authors.affiliation: Laboratory of Neuro-oncology, Croatian Institute for Brain Research, School of Medicine University of Zagreb, Zagreb, Croatia.
authors.forename: Martina
authors.initials: M
authors.lastname: Zeljko
authors.forename: Nives
authors.initials: N
authors.lastname: Pecina-Slaus
authors.forename: Tamara Nikuseva
authors.initials: TN
authors.lastname: Martic
authors.forename: Vesna
authors.initials: V
authors.lastname: Kusec
authors.forename: Vili
authors.initials: V
authors.lastname: Beros
authors.forename: Davor
authors.initials: D
authors.lastname: Tomas
mesh_terms: D022005:Adherens Junctions / Q000235:genetics / Q000378:metabolism*; D015703:Antigens, CD; D001932:Brain Neoplasms / Q000235:genetics / Q000556:secondary*; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D051176:beta Catenin