Coexpression of platelet-derived growth factor alpha and beta receptors on medulloblastomas and other primitive neuroectodermal tumors is consistent with an immature stem cell and neuronal derivation.
Medulloblastomas and related childhood primitive neuroectodermal tumors (PNET) are currently thought to originate from a multipotent stem cell that can give rise to a variety of different tumor types, representing different lines of differentiation and stages of maturation of the original stem cell. The proliferation and differentiation of different cell types in the central nervous system are influenced by growth factors, such as platelet-derived growth factor (PDGF). In this study, we investigated the expression of the two types of PDGF receptors, alpha and beta, on 14 cases of PNET by immunohistochemistry and in situ hybridization. To characterize the tumor cells according to their differentiation and maturation, we performed immunohistochemistry with Ab against several members of the intermediate filament family, such as neurofilament, glial fibrillary acidic protein, vimentin, and the embryonal marker nestin. For the cerebral PNET, we found that the phenotype of multidirectional differentiation (with coexpression of neurofilament, glial fibrillary acidic protein, vimentin, and in some cases nestin) was associated with the expression of both PDGF alpha and beta receptors on the tumor cells. Medulloblastomas (i.e., cerebellar PNET), however, often showed the phenotype of partially committed neuron-like precursor cells, and this was associated with the predominant expression of PDGF alpha receptors on the tumor cells. Our findings show that the PDGF alpha receptor, previously known to play a role in the normal development of cells of the glial lineage, either exclusively or in combination with the PDGF beta receptor, is expressed on tumor cells of neuronal derivation. This "aberrant" expression of PDGF alpha receptors on PNET may reflect a feature of the malignant phenotype of these tumors. Further studies are needed to study the biologic effects of PDGF-A and its receptor in PNET.
Smits
A
A
Department of Neurology, University Hospital, Uppsala, Sweden.
van Grieken
D
D
Hartman
M
M
Lendahl
U
U
Funa
K
K
Nistér
M
M
D001932:Brain Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D002528:Cerebellar Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D007382:Intermediate Filaments / Q000737:chemistry; D008527:Medulloblastoma / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis*
D017479:Receptors, Platelet-Derived Growth Factor