Prognostic Significance of R or2 and W nt5a Expression in Medulloblastoma

Medulloblastoma ( MB ) is a clinically and biologically heterogeneous group of tumors, and currently classified into four molecular subgroups ( W nt, S hh, Group 3 and Group 4). Intracellular signaling of the W nt 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 W nt‐5a and R or2 , 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. W nt5a and R or2 were immunopositive in 20 (29.4%) and 35 (51.5%) of 68 cases, respectively. There were positive associations among protein expressions of W nt5a, R or2 and β‐catenin. R or2 m R NA levels were well correlated with immunoexpression. R or2 m RNA expression was significantly associated with CTNNB 1 mutation. High R or2 m RNA expression was an independent favorable prognostic factor. In conclusion, our study demonstrates the first attempt to identify W nt5a and R or2 as additional mechanisms contributing to dysregulation of the non‐canonical WNT signaling pathway in MB . R or2 may play a role as an oncosuppressor in MB .