title: Activation of beta-catenin is a late event in the pathogenesis of nephroblastomas and rarely correlated with genetic changes of the APC gene.
abstract: OBJECTIVE
  Activation of β-catenin has been identified as a possible mechanism for the development of nephroblastomas. In our study we investigated whether this activation occurs already in precursor lesions of nephroblastomas, called nephrogenic rests (NRs). Inactivation of the adenomatous polyposis coli (APC) protein is an important regulatory mechanism of activating β-catenin. We clarified the role of APC by assessing loss of heterozygosity (LOH) and possible mutations within the genomic region.
  
  
  METHODS
  Activation of β-catenin was examined by immunohistochemistry identifying nuclear translocation. Two polymorphic loci of the APC gene were investigated for LOH and sequence analysis was performed for the mutation cluster region of the APC gene on formalin fixed, paraffin embedded samples.
  
  
  RESULTS
  Four of the 18 nephroblastomas available for immunohistochemistry exhibited nuclear staining of β-catenin, but none of the NRs. Analysis of LOH revealed 14 homozygous samples, 10 heterozygous tumours and six tumours exhibiting LOH of the APC gene. One blastema-type nephroblastoma showed nuclear localisation of β-catenin in conjunction with LOH of the APC gene. Analysis of 12 nephroblastomas revealed no sequence aberration.
  
  
  CONCLUSIONS
  Our results indicate that nuclear activation of β-catenin is a late event in the tumorigenesis of nephroblastomas coinciding in some tumours with LOH of the APC gene.
authors.affiliation: Department of Pathology General Hospital and Paracelsus Medical University Salzburg, Salzburg.
authors.forename: Christine
authors.initials: C
authors.lastname: Grill
authors.forename: Sandra
authors.initials: S
authors.lastname: Sunitsch
authors.forename: Martina
authors.initials: M
authors.lastname: Hatz
authors.forename: Cornelia
authors.initials: C
authors.lastname: Hauser-Kronberger
authors.forename: Ivo
authors.initials: I
authors.lastname: Leuschner
authors.forename: Gerald
authors.initials: G
authors.lastname: Hoefler
authors.forename: Barbara
authors.initials: B
authors.lastname: Guertl
mesh_terms: D017491:Genes, APC; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009396:Wilms Tumor / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin