Abstract
Background: Neuron glial antigen 2 or chondroitin sulphate proteoglycan 4 (NG2/CSPG4) is expressed by immature precursors/progenitor cells and is possibly involved in malignant cell transformation. The aim of this study was to investigate its role on the progression and survival of sixty-one adult gliomas and nine glioblastoma (GB)-derived cell lines. Methods: NG2/CSPG4 protein expression was assessed by immunohistochemistry and immunofluorescence. Genetic and epigenetic alterations were detected by molecular genetic techniques. Results: NG2/CSPG4 was frequently expressed in IDH-mutant/1p19q-codel oligodendrogliomas (59.1%) and IDH-wild type GBs (40%) and rarely expressed in IDH-mutant or IDH-wild type astrocytomas (14.3%). Besides tumor cells, NG2/CSPG4 immunoreactivity was found in the cytoplasm and/or cell membranes of reactive astrocytes and vascular pericytes/endothelial cells. In GB-derived neurospheres, it was variably detected according to the number of passages of the in vitro culture. In GB-derived adherent cells, a diffuse positivity was found in most cells. NG2/CSPG4 expression was significantly associated with EGFR gene amplification (p = 0.0005) and poor prognosis (p = 0.016) in astrocytic tumors. Conclusion: The immunoreactivity of NG2/CSPG4 provides information on the timing of the neoplastic transformation and could have prognostic and therapeutic relevance as a promising tumor-associated antigen for antibody-based immunotherapy in patients with malignant gliomas.
Highlights
Neuron glial antigen 2 (NG2) or chondroitin sulphate proteoglycan 4 (CSPG4) is expressed in the developing and adult central nervous system (CNS)
The aim of the present study was to analyze the role of NG2/CSPG4 in relation to malignant progression and prognosis in a series of 61 adult human gliomas of different molecular subtypes and in nine GB-derived cell lines At the protein level, NG2/CSPG4 expression was evaluated by immunohistochemistry (IHC) in tumor tissues and by immunofluorescence (IF) in cell lines
In the healthy nervous tissue, NG2/CSPG4 was expressed in the cytoplasm of neurons, whereas it was not found in glial cells or endothelial cells (ECs)
Summary
Neuron glial antigen 2 (NG2) or chondroitin sulphate proteoglycan 4 (CSPG4) is expressed in the developing and adult central nervous system (CNS). As a matter of fact, in vitro NG2-glia can differentiate into type 2 astrocytes [11,12,13]; under specific cell culture conditions, oligodendrocyte-type 2 astrocyte (O2A). NG2/CSPG4 immunoreactivity was found in the cytoplasm and/or cell membranes of reactive astrocytes and vascular pericytes/endothelial cells. NG2/CSPG4 expression was significantly associated with EGFR gene amplification (p = 0.0005) and poor prognosis (p = 0.016) in astrocytic tumors. Conclusion: The immunoreactivity of NG2/CSPG4 provides information on the timing of the neoplastic transformation and could have prognostic and therapeutic relevance as a promising tumor-associated antigen for antibody-based immunotherapy in patients with malignant gliomas
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