von Deimling A, Kleihues P, Saremaslani P, Yasargil M G, Spoerri O, Südhof T C, Wiestler O D
Department of Pathology, University of Zürich, Switzerland.
Lab Invest. 1991 Apr;64(4):585-91.
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.
中枢神经细胞瘤是一种最近才被确认的发生于年轻人的罕见幕上脑肿瘤，其特点是位于脑室内，临床过程通常为良性。为了阐明这种肿瘤的组织发生和分化潜能，我们对4例中枢神经细胞瘤进行了免疫细胞化学和分子生物学研究。通过免疫细胞化学和免疫印迹发现，所有肿瘤均表达神经元特异性烯醇化酶和突触素。蛋白质印迹法还显示，在一些石蜡切片上对这些标记抗原无免疫反应性的神经细胞瘤中，存在突触囊泡蛋白、突触素I、神经丝蛋白和胶质纤维酸性蛋白的表达。在相邻切片上用抗突触素和胶质纤维酸性蛋白抗体进行的免疫细胞化学反应显示，个别肿瘤细胞中存在共表达。在所研究的2例中枢神经细胞瘤中未检测到pp60src蛋白酪氨酸激酶的神经元形式，该癌基因产物在中枢神经系统神经元中特异性表达。N-myc是一种在儿童神经母细胞瘤中经常扩增的原癌基因，在所有中枢神经细胞瘤中均以单拷贝基因形式存在，这表明该基因的扩增与中枢神经细胞瘤的发病机制无关。根据突触发生的超微结构证据，我们得出结论，中枢神经细胞瘤是一种神经外胚层肿瘤，具有一致的神经元分化倾向。由于这些肿瘤保留了额外的胶质细胞分化潜能，我们提出其起源于脑室周围基质中的双能祖细胞，在哺乳动物脑中，这种祖细胞在成年期一直存在。
