Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations

Craniopharyngioma is a rare tumor occurring in the sellar region comprising 3% of all intracranial tumors. To elucidate the contribution of beta-catenin gene mutation to tumorigenesis, we examined genetic alterations and expression of beta-catenin in 10 cases of adamantinomatous and 6 cases of papillary craniopharyngiomas. Beta-catenin gene mutations were found in all of the adamantinomatous and none of the papillary craniopharyngiomas. Immunohistochemically, all cases of adamantinomatous craniopharyngioma showed cytoplasmic and nuclear expression of beta-catenin. In contrast, papillary craniopharyngiomas showed exclusively membranous expression. The results suggest that adamantinomatous- and papillary-type craniopharyngiomas are not only clinicopathologically, but also genetically, distinctive variants. Mutation of the beta-catenin gene therefore seems to play an important role in the tumorigenesis of adamantinomatous craniopharyngioma. Among the adamantinomatous-type tumors, beta-catenin-positive mesenchymal cells were observed in two cases. Microdissection-based mutational analysis revealed that these mesenchymal cells also harbor the same beta-catenin gene mutations as those of epithelial cells, suggesting their tumorous nature. Thus, at least a subset of adamantinomatous craniopharyngioma is considered to be biphasic.