Expression of the neurotrophin receptor p75(NTR) in medulloblastomas is correlated with distinct histological and clinical features: Evidence for a medulloblastoma subtype derived from the external granule cell layer

Medulloblastomas (MBs) are primitive neuroectodermal tumors (PNET) of the c erebellum. They represent the most frequent malignant pediatric brain tumor s, but their origin still remains unresolved and controversial. IMB cells c orrespond to different stages of neural development and differentiation as illustrated by their expression of neuronal and glial markers. In the prese nt study, we examined the expression pattern of the common low-affinity neu rotrophin receptor p75(NTR) in a series of 167 MBs by immunohistochemistry. While p75(NTR) was present in only 17% of classic MBs (CMB), we found expr ession of p75(NTR) in all desmoplastic (nodular) MBs (DMB) examined, and in 71% of those MBs with a significant desmoplastic component. Furthermore, b oth desmoplastic histology and p75(NTR) expression were present preferentia lly in those tumors of adolescents and adults that are frequently located l aterally in the cerebellar hemispheres. In DMBs, p75(NTR) was expressed pre dominantly in the proliferative, reticulin-rich areas, which may show coexp ression of GFAP. In the pale islands of DMB, p75(NTR) was expressed only we akly or was absent. The expression pattern showed an inverse relation to th at of the synaptic vesicle protein synaptophysin that was predominant in p7 5(NTR) negative classic MBs. Since the neurotrophin receptor p75(NTR) is ex pressed in cells of the external granule cell layer (EGL) of the fetal cere bellum, our findings suggest that progenitor cells of the EGL are the cellu lar origin of a distinct subset of MB, namely the desmoplastic variant and MBs with a significant desmoplastic component.