Distinct expression pattern of microtubule-associated protein-2 in human oligodendrogliomas and glial precursor cells

Microtubule-associated protein 2 (MAP2), a protein linked to the neuronal c ytoskeleton in the mature central nervous system (CNS), has recently been i dentified in glial precursors indicating a potential role during glial deve lopment. In the present study, we systematically analyzed the expression of MAP2 in a series of 237 human neuroepithelial tumors including paraffin-em bedded specimens and tumor tissue microarrays from oligodendrogliomas, mixe d gliomas, astrocytomas, glioblastomas, ependymomas, as well as dysembryopl astic neuroepithelial tumors (DNT), and central neurocytomas. In addition, MAP2-immunoreactive precursor cells were studied in the developing human br ain. Three monoclonal antibodies generated against MAP2A-B or MAP2A-D isofo rms were used. Variable immunoreactivity for MAP2 could be observed in all gliomas with the exception of ependymomas. Oligodendrogliomas exhibited a c onsistently strong and distinct pattern of expression characterized by peri nuclear cytoplasmic staining without significant process labeling. Tumor ce lls with immunoreactive bi- or multi-polar processes were mostly encountere d in astroglial neoplasms, whereas the small cell component in neurocytomas and DNT was not labeled. These features render MAP2 immunoreactivity a hel pful diagnostic tool for the distinction of oligodendrogliomas and other ne uroepithelial neoplasms. RT-PCR, western blot analysis, and in situ hybridi zation confirmed the expression of MAP2A-C (including the novel MAP2+ 13 tr anscript) in both oligodendrogliomas and astrocytomas. Double fluorescent l aser scanning microscopy showed that GFAP and MAP2 labeled different tumor cell populations. In embryonic human brains, MAP2-immunoreactive glial prec ursor cells were identified within the subventricular or intermediate zones . These precursors exhibit morphology closely resembling the immunolabeled neoplastic cells observed in glial tumors. Our findings demonstrate MAP2 ex pression in astrocytic and oligodendroglial neoplasms. The distinct pattern of immunoreactivity in oligodendrogliomas may be useful as a diagnostic to ol. Since MAP2 expression occurs transiently in migrating immature glial ce lls, our findings are in line with an assumed origin of diffuse gliomas fro nt glial precursors.