Expression of the neurotrophin receptor p75NTR in medulloblastomas is correlated with distinct histological and clinical features: evidence for a medulloblastoma subtype derived from the external granule cell layer

Abstract

Medulloblastomas (MBs) are primitive neuroectodermal tumors (PNET) of the cerebellum. They represent the most frequent malignant pediatric brain tumors, but their origin still remains unresolved and controversial. MB cells correspond to different stages of neural development and differentiation as illustrated by their expression of neuronal and glial markers. In the present study, we examined the expression pattern of the common low-affinity neurotrophin receptor p75NTR in a series of 167 MBs by immunohistochemistry. While p75NTR was present in only 17% of classic MBs (CMB), we found expression of p75NTR in all desmoplastic (nodular) MBs (DMB) examined, and in 71% of those MBs with a significant desmoplastic component. Furthermore, both desmoplastic histology and p75NTR expression were present preferentially in those tumors of adolescents and adults that are frequently located laterally in the cerebellar hemispheres. In DMBs, p75NTR was expressed predominantly in the proliferative, reticulin-rich areas, which may show coexpression of GFAP. In the pale islands of DMB, p75NTR was expressed only weakly or was absent. The expression pattern showed an inverse relation to that of the synaptic vesicle protein synaptophysin that was predominant in p75NTR negative classic MBs. Since the neurotrophin receptor p75NTR is expressed in cells of the external granule cell layer (EGL) of the fetal cerebellum, our findings suggest that progenitor cells of the EGL are the cellular origin of a distinct subset of MB, namely the desmoplastic variant and MBs with a significant desmoplastic component.