Activation of beta-catenin is a late event in the pathogenesis of nephroblastomas and rarely correlated with genetic changes of the APC gene

SummaryAimsActivation 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 p-catenin. We clarified the role of APC by assessing loss of heterozygosity (LOH) and possible mutations within the genomic region.MethodsActivation 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.ResultsFour 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 blastematype nephroblastoma showed nuclear localisation of β-catenin in conjunction with LOH of the APC gene. Analysis of 12 nephroblastomas revealed no sequence aberration.ConclusionOur results indicate that nuclear activation of p-catenin is a late event in the tumorigenesis of nephroblastomas coinciding in some tumours with LOH of the APC gene.