Neuronal differentiation associated with Gli3 expression predicts favorable outcome for patients with medulloblastoma.

Medulloblastoma (MB) is a malignant cerebellar tumor arising in children, and its ontogenesis is regulated by Sonic Hedgehog (Shh) signaling. No data are available regarding the correlation between expression of Gli3, a protein lying downstream of Shh, and neuronal differentiation of MB cells, or the prognostic significance of these features. We re-evaluated the histopathological features of surgical specimens of MB taken from 32 patients, and defined 15 of them as MB with neuronal differentiation (ND), three as MB with both glial and neuronal differentiation (GD), and 14 as differentiation-free (DF) MB. Gli3-immunoreactivity (IR) was evident as a clear circular stain outlining the nuclei of the tumor cells. The difference in the frequency of IR between the ND+GD (94.4%) and DF (0%) groups was significant (P < 0.001). The tumor cells with ND showed IR for both Gli3 and neuronal nuclei. Ultrastructurally, Gli3-IR was observed at the nuclear membrane. The overall survival and event-free survival rates of the patients in the ND group were significantly higher than those in the other groups. The expression profile of Gli3 is of considerable significance, and the association of ND with this feature may be prognostically favorable in patients with MB.