title: Genetic and protein changes of E-cadherin in meningiomas.
abstract: OBJECTIVE
  The molecular mechanisms and candidate genes involved in development of meningiomas still needs investigation and elucidation.
  
  
  METHODS
  In the present study 60 meningiomas were analyzed regarding changes of tumor suppressor gene E-cadherin (CDH1), a component of adherens junction and an indirect modulator of the wnt signaling. Gene instability was tested by polymerase chain reaction/loss of heterozygosity (LOH) method. Protein expression was analyzed by immunohistochemistry.
  
  
  RESULTS
  The results of our analysis showed altogether 32% of samples with LOH of the CDH1 gene. Interestingly, another type of genomic instability was detected; replication error-positive samples (RER+). Three out of 28 heterozygous samples were RER+ (11%). The instability is the result of impaired cellular mismatch repair. Fibrous and angiomatous cases showed higher percent of genetic changes, 67 and 75%, respectively. Immunostaining showed that overall 73% of samples had downregulation of E-cadherin expression. Intense downregulation of E-cadherin was noticed in tumors with grades II and III. Five out of nine samples with LOH were accompanied with the downregulation of E-cadherin protein expression (56%). One RER+ sample had lower expression of E-cadherin. We noticed that 36.4% of samples with lower E-cadherin expression had beta-catenin located in the nucleus. Also, 75% of samples with genomic instabilities had beta-catenin in the nucleus. Our findings demonstrated that there is significant association between the genetic changes of CDH1 and the nuclear localization of beta-catenin protein (chi(2) = 5.25, df = 1, P < 0.022). Beta-catenin was progressively upregulated from meningothelial to atypical, while 60% of anaplastic showed upregulation and nuclear localization of the protein.
  
  
  CONCLUSIONS
  Our results suggest that genetic instabilities of the E-cadherin gene have a role in meningioma development and progression. Detected microsatellite instability indicates that mismatch repair may also be targeted in meningioma.
authors.affiliation: Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Croatia. nina@mef.hr
authors.forename: Nives
authors.initials: N
authors.lastname: Pećina-Slaus
authors.forename: Tamara
authors.initials: T
authors.lastname: Nikuseva Martić
authors.forename: Adam Jakov
authors.initials: AJ
authors.lastname: Deak
authors.forename: Martina
authors.initials: M
authors.lastname: Zeljko
authors.forename: Reno
authors.initials: R
authors.lastname: Hrasćan
authors.forename: Davor
authors.initials: D
authors.lastname: Tomas
authors.forename: Vesna
authors.initials: V
authors.lastname: Musani
mesh_terms: D000328:Adult; D000368:Aged; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D042822:Genomic Instability; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000378:metabolism; D008579:Meningioma / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D051176:beta Catenin / Q000235:genetics
chemical_list: D015820:Cadherins; D051176:beta Catenin