Prognostic Significance of Ror2 and Wnt5a Expression in Medulloblastoma

Abstract

Medulloblastoma (MB) is a clinically and biologically heterogeneous group of tumors, and currently classified into four molecular subgroups (Wnt, Shh, Group 3 and Group 4). Intracellular signaling of the Wnt pathway has been divided into two classes: the "canonical" and the "non-canonical" signaling pathway. The canonical signaling pathway is a well-established, β-catenin-dependent signaling pathway in MB. In contrast, very little research about the non-canonical WNT signaling pathway in MB exists. In order to identify the roles of Wnt-5a and Ror2, two non-canonical WNT pathway-related genes, we studied 76 cases of MB with immunohistochemistry and quantitative real-time PCR and correlated the results with clinicopathological and other molecular parameters and prognosis. Wnt5a and Ror2 were immunopositive in 20 (29.4%) and 35 (51.5%) of 68 cases, respectively. There were positive associations among protein expressions of Wnt5a, Ror2 and β-catenin. Ror2 mRNA levels were well correlated with immunoexpression. Ror2 mRNA expression was significantly associated with CTNNB1 mutation. High Ror2 mRNA expression was an independent favorable prognostic factor. In conclusion, our study demonstrates the first attempt to identify Wnt5a and Ror2 as additional mechanisms contributing to dysregulation of the non-canonical WNT signaling pathway in MB. Ror2 may play a role as an oncosuppressor in MB.