Microtubule-associated protein 2 (MAP2), a
protein linked to the neuronal cytoskeleton in the mature central nervous system (CNS), has recently been identified in glial precursors indicating a potential role during glial development. In the present study, we systematically analyzed the expression of MAP2 in a series of 237 human
neuroepithelial tumors including
paraffin-embedded specimens and
tumor tissue microarrays from
oligodendrogliomas,
mixed gliomas,
astrocytomas,
glioblastomas,
ependymomas, as well as dysembryoplastic
neuroepithelial tumors (
DNT), and
central neurocytomas. In addition, MAP2-immunoreactive precursor cells were studied in the developing human brain. Three
monoclonal antibodies generated against MAP2A-B or MAP2A-D
isoforms were used. Variable immunoreactivity for MAP2 could be observed in all
gliomas with the exception of
ependymomas.
Oligodendrogliomas exhibited a consistently strong and distinct pattern of expression characterized by perinuclear cytoplasmic staining without significant process labeling.
Tumor cells with immunoreactive bi- or multi-polar processes were mostly encountered in astroglial
neoplasms, whereas the small cell component in
neurocytomas and
DNT was not labeled. These features render MAP2 immunoreactivity a helpful diagnostic tool for the distinction of
oligodendrogliomas and other
neuroepithelial neoplasms. RT-PCR, Western blot analysis, and in situ hybridization confirmed the expression of MAP2A-C (including the novel MAP2+ 13 transcript) in both
oligodendrogliomas and
astrocytomas. Double fluorescent
laser scanning microscopy showed that GFAP and MAP2 labeled different
tumor cell populations. In embryonic human brains, MAP2-immunoreactive glial precursor 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 expression in astrocytic and oligodendroglial
neoplasms. The distinct pattern of immunoreactivity in
oligodendrogliomas may be useful as a diagnostic tool. Since MAP2 expression occurs transiently in migrating immature glial cells, our findings are in line with an assumed origin of diffuse
gliomas from glial precursors.