Analysis of β-Catenin Expression and Exon 3 Mutations in Pediatric Sporadic Aggressive Fibromatosis

Abstract

Aggressive fibromatosis is a benign tumor with a high recurrence rate after surgical resection, particularly in children. Abnormal regulation of β-catenin in the presence or absence of a change of genotype has been identified in adult sporadic aggressive fibromatosis. However, the status of β-catenin expression and mutation remains unclear in pediatric patients. The present study was designed to analyze the expression and mutation status of β-catenin in pediatric aggressive fibromatosis. B-catenin expression was analyzed by immunohistochemistry in 32 samples from pediatric patients withaggressive fibromatosis (21 recurrent cases and 11 primary-onset cases) and 15 control subjects. Somatic point mutations in β-catenin exon 3 were identified by sequencing of polymerase chain reaction products. Nuclear expression of β-catenin was detected in 94% (30/32) of aggressive fibromatosis samples and 13% (2/15) of control samples (P < 0.001). Mutations in exon 3 of the β-catenin gene were identified in 78% (25/32) of aggressive fibromatosis samples (19/21 recurrent cases, 6/11 primary-onset cases; P = 0.032). The primary mutation in the recurrent cases occurred at codon 45 (S45F), while codon 41 (T41A) was most frequently mutated in the primary-onset cases (P = 0.002). Abnormal expression of β-catenin appears to occur frequently in pediatric aggressive fibromatosis. Muftations in exon 3 of the β-catenin gene, particularly the S45F mutation, may represent risk factors for recurrence in pediatric patients and could potentially be used as prognostic factors.