Additional adjustment for tumor size yielded a P-value of 0.082 with hazard ratio's of 0.83 [95% confidence interval (CI) 0.48-1.42), 0.37 (95% CI 0.12-1.14), and 0.44 (95% CI 0.21-0.92) for T41A, S45P and WT DTF tumors compared to S45F DTF tumors.
Tumor DNA analysis revealed a heterozygous ACC-to-GCC missense mutation in codon 41 (T41A) and a TCT-to-CCT missense mutation in codon 45 (S45P) of exon 3 of the beta-catenin gene that was confirmed at the cDNA level.
Molecular analysis of microdissected cells from the left tumour revealed the same S45P CTNNB1 mutation in blastema, tubuli, stroma and muscle, and a different CTNNB1 mutation (T41A) in stromal cells isolated from another area of the same slide.
Other three mutations were detected in three of five multiple tumors developed in the bilateral WT patient; a mutation of Delta45 in one of two tumors in the right kidney, and Ser45Cys (TCT --> TGT) and Ser45Pro (TCT --> CCT) in two of three tumors in the left kidney.
Nuclear and/or cytoplasmic localization of beta-catenin, a potential indicator of wnt pathway activation, was seen focally within roughly one third of the tumors, though a clonal somatic mutation in beta-catenin was found in only one case (codon 45 Ser-->Pro).