Abstract

Background: Intralobar nephrogenic rests (ILNRs) are precursor lesions for Wilms tumours and are associated with WT1 gene mutations. ILNR-associated Wilms tumours have a co-clustering of WT1 and β-catenin (CTNNB1) mutations and unique histological features characterised by a stromal-predominant histology.

Aim: To determine the order in which WT1 and CTNNB1 mutations occur to understand the ILNR–Wilms tumour sequence.

Methods: Of nine Wilms tumours with WT1 and CTNNB1 mutations, three ILNRs lesions in two Wilms tumours were available for analysis of WT1 and CTNNB1 mutations using microdissection. Immunohistochemistry was also performed to investigate how the mutations in β-catenin alter the localisation in Wilms tumour development.

Results:WT1 mutations were present in the ILNRs, however CTNNB1 mutations were absent. Immunohistochemistry for WT1 confirmed inactivation of WT1 in both ILNRs and Wilms tumours. Both the ILNRs and the associated Wilms tumours had similar immunostaining patterns for β-catenin in the blastemal and epithelial components. Although rhabdomyoblasts were not included in ILNRs, the associated Wilms tumours showed rhabdomyogenic differentiation with a positive β-catenin nuclear staining.

Conclusions: The results suggest that CTNNB1 mutation is a later event in Wilms tumourigenesis. CTNNB1 mutations might be associated with rhabdomyogenesis.