Neurotrophin and neurotrophin receptor proteins in medulloblastomas and other primitive neuroectodermal tumors of the pediatric central nervous system.

Primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS) are poorly understood childhood neoplasms, and medulloblastomas are the most common pediatric PNETs. Neoplastic cells in medulloblastomas and other PNETs resemble progenitor cells of the developing central nervous system, but they also may exhibit the molecular phenotype of immature neurons or glia. As neurotrophins play a role in regulating differentiation, proliferation, and cell death in the normal developing central nervous system, and recent evidence suggests that neurotrophins may influence the behavior of medulloblastomas, we studied 29 PNET biopsy samples (27 of which were posterior fossa medulloblastomas) by immunobistochemistry using antibodies specific for each of the major high affinity neurotrophin receptor proteins, ie, TrkA, TrkB, and TrkC. A subset of these tumors also was examined by Western blot. Immunoreactive TrkA, TrkB, and TrkC were observed in neoplastic cells in 8 (27%), 18 (62%), and 14 (48%) of these PNETs, respectively. Additional immunohistochemical studies of a subset of these PNETs using antibodies to neurotrophins that primarily activate TrkB and TrkC, ie, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5, showed that immunoreactive brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 were detected in 22, 9, and 19% of these PNET biopsies, respectively. Finally, 19 pediatric brain tumors other than these PNETs also were studied here, and they expressed these neurotrophins and their receptors to a variable extent. The demonstration here that neurotrophins and their cognate receptor proteins are expressed in PNETs as well as in other pediatric brain tumors may imply that signal transduction pathways mediated by neurotrophins and/or their receptors influence the induction or progression of these common childhood neoplasms.