Neurotrophin Receptor Expression in Primitive Neuroectodermal Tumors of the Brain in Childhood

中枢神经系统的原始神经外胚层肿瘤（PNET）是一种鲜为人知的儿童肿瘤，髓母细胞瘤是最常见的儿童PNETs。髓母细胞瘤和其他PNETs中的肿瘤细胞类似于发育中的中枢神经系统的祖细胞，但它们也可能表现出未成熟神经元或胶质细胞的分子表型。由于神经营养因子在正常发育的中枢神经系统中发挥调节分化、增殖和细胞死亡的作用，并且最近的证据表明神经营养因子可能影响成神经管细胞瘤的行为，我们通过免疫组织化学方法研究了29个PNET活检样本（其中27个为后窝成神经管细胞瘤），使用针对每种主要高亲和力神经营养因子受体蛋白（即TrkA和TrkC）的抗体。这些肿瘤的一个子集也被Western blot检测。在这些PNETs中，分别在20%、50%的肿瘤细胞中观察到免疫反应性TrkA、TrkB和TrkC。TrkA和TrkB主要存在于滤泡结构中，TrkC主要存在于未分化的肿瘤细胞中，未存在于滤泡结构中。使用主要激活TrkB和TrkC的神经营养因子（即脑源性神经营养因子、神经营养因子-3和神经营养因子-4/5）的抗体对这些PNETs的一个子集进行免疫组化研究，结果显示，在这些PNET活检中，分别有20%、10%和20%检测到免疫反应性脑源性神经营养因子、神经营养因子-3和神经营养因子-4/5。神经营养因子及其同源受体蛋白在PNETs中表达的证明可能暗示由神经营养因子和/或其受体介导的信号转导通路影响这些常见儿童肿瘤的诱导或进展。

Primitive neuroectodermal tumor (PNET) of the Central Nervous System 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 immunohistochemisty using antibodies specific for each of the major high affinity neurotrophin receptor proteins, ie, TrkA,and TrkC.A subset of these tumors also was examined by Western blot. Immunoreactive TrkA,TrkB,and TrkC were observed in neoplastic cells in 20%, 50% of these PNETs, respectively. TrkA and TrkB were mainly observed in follicular structures, and TrkC was observed in undifferentiated tumor cells, not in follicular structures. 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 20,10, and 20% of these PNET biopsies, respectively.The demonstration here that neurotrophins and their cognate receptor proteins are expressed in PNETs may immply that signal transduction pathways mediated by neurotrophins and/or their receptors influence the induction or progression of these common childhood neoplasms.