Frequent beta-catenin mutation and cytoplasmic/nuclear accumulation in pancreatic solid-pseudopapillary neoplasm

Significance of Wnt signaling with beta-catenin mutations on solid-pseudopapillary neoplasm (SPN) of the pancreas was studied by immunohistochemistry and molecular analysis. On immunohistochemistry, all 18 SPNs tested showed diffuse cytoplasmic/nuclear positivity for beta-catenin. Upon direct DNA sequencing of exon 3 of the beta-catenin gene, 15 (83%) of the 18 SPNs showed 1-bp missense mutation in codons 32 (5 cases), 33 (3 cases), 34 (3 cases), 37 (3 cases), and 41 (1 case). Immunoreactivity for cyclin D1, one of the intranuclear targets of beta-catenin complexes, was found in tumor cells of more than half the tumor cells of all of the 18 SPNs. The present study strongly suggested a significant role of Wnt signaling, mostly associated with beta-catenin mutations in the tumorigenesis of SPN.