Distinct expression of the histon methyltransferase EZH2 in β-catenin accumulating cells of adamantinomatous craniopharyngiomas

Abstract

Objectives: As histone methyltransferase of the polycomb repressive complex 2 (PRC2), EZH2 mediates trimethylation of histone H3at lysine 27 (H3K27me3), which entails epigenetic repression/silencing of genes e.g. inhibitors of the Wnt signaling pathway. Craniopharyngiomas (CP) represent a heterogeneous group of benign epithelial tumors of the sellar region, consisting of a papillary (papCP) and an adamantinomatous (adaCP) variant. Aberrant Wnt signaling has been identified as a molecular hallmark of adaCPs, characterized by activating mutations in the β-catenin gene as well as nuclear β-catenin accumulations. Methods: Herein, we analyzed the expression pattern of EZH2 in a cohort of 61 adaCP and 22 papCP, utilizing immunohistochemistry as well as double immunofluorescence staining of EZH2 and β-catenin. Furthermore, we determined EZH2 mRNA expression in 17 adaCP and 8 papCP, applying TaqMan gene expression assays of total tumor RNA. Results: EZH2 is heterogeneously distributed in both CP subtypes; nevertheless, the degree of immunoreactivity seems to be obviously enhanced in adaCP areas with nuclear β-catenin accumulations. Additionally, EZH2 and β-catenin double immunofluorescence staining confirmed co-localization of both proteins in whirl like tumor cell clusters. However, both CP subtypes do not significantly differ in overall EZH2 mRNA expression level. Conclusion: Our data suggest an impact of epigenetic regulatory mechanisms in adaCP cells with activated Wnt signaling. Affected genes need to be identified in further studies.