Histogenesis and differentiation potential of central neurocytomas

Abstract

The central neurocytoma, a recently identified rare supratentorial brain tumor in young adults, is characterized by intraventricular location and a usually benign clinical course. In order to elucidate the histogenesis and differentiation potential of this neoplasm, we have undertaken an immunocytochemical and molecular biological study of four central neurocytomas. It was found by immunocytochemistry and immunoblotting that all tumors express neuron-specific enolase and synaptophysin. Western blots also revealed expression of the synaptic vesicle protein, synapsin I, neurofilament protein and glial fibrillary acidic protein in several neurocytomas which failed to exhibit immunoreactivity to these marker antigens on paraffin sections. Immunocytochemical reactions with antibodies to synaptophysin and glial fibrillary acidic protein on adjacent sections demonstrated coexpression in individual tumor cells. The neuronal form of the pp60src protein-tyrosine kinase, an oncogene-product specifically expressed in central nervous system neurons, was not detectable in two central neurocytomas investigated. N-myc, a proto-oncogene frequently amplified in childhood neuroblastomas, was present as a single copy gene in all central neurocytomas, indicating that amplification of this gene is not involved in the pathogenesis of the central neurocytoma. In accordance with ultrastructural evidence of synaptogenesis, we conclude that the central neurocytoma is a neuroectodermal tumor with consistent commitment for neuronal differentiation. Since these tumors retain a potential for additional glial differentiation, we propose an origin from bipotential progenitor cells in the periventricular matrix, which in the mammalian brain persists throughout adult life.