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

作者：Grill Christine; Sunitsch Sandra; Hatz Martina; Hauser Kronberger Cornelia; Leuschner Ivo; Hoefler Gerald; Guertl Barbara^*

来源：Pathology, 2011, 43(7): 702-706.

DOI：10.1097/PAT.0b013e32834bf65c

• beta-catenin
• APC
• immunohistochemistry
• LOH
• mutation analysis
• nephroblastoma
• nephrogenic rest

Aims: Activation of beta-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 beta-catenin. We clarified the role of APC by assessing loss of heterozygosity (LOH) and possible mutations within the genomic region.
Methods: Activation of beta-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 beta-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 beta-catenin in conjunction with LOH of the APC gene. Analysis of 12 nephroblastomas revealed no sequence aberration.
Conclusion: Our results indicate that nuclear activation of beta-catenin is a late event in the tumorigenesis of nephroblastomas coinciding in some tumours with LOH of the APC gene.

• 出版日期2011-12