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Frequent ß-Catenin Mutation and Cytoplasmic/Nuclear Accumulation in Pancreatic Solid-Pseudopapillary Neoplasm

Division of Pathology, Kanagawa Children’s Medical Center, Yokohama 232 [Y. T., K. K., R. I., T. M., Y. N.]; Department of Pathology, Okayama University, Okayama [K. N.]; Department of Pathology, Fukushima Prefectural University, Fukushima [H. H.]; Department of Environmental Medicine, Nihon Medical School, Nihon [N. N.]; Department of Pediatric Surgery, Hokkaido University, Hokkaido [F. S., N. K.]; and Division of Pathology, Osaka City General Medical Center, Osaka [Y. K.], Japan

Significance of Wnt signaling with ß-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 ß-catenin. Upon direct DNA sequencing of exon 3 of the ß-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 ß-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 ß-catenin mutations in the tumorigenesis of SPN.

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