Olig2 and CD99 are useful negative markers for the diagnosis of brain tumors.

Olig2, a member of the group of basic helix-loop-helix transcription factors, is innately expressed in oligodendrocytes. In the neoplastic condition, Olig2 is widely expressed in astrocytomas and oligodendrogliomas, but its expression in ependymomas remains poorly documented. A total of 59 brain tumors including 16 ependymomas, 32 astrocytomas, and 11 oligodendrogliomas were immunohistochemically studied for the expression of Olig2 as well as other markers including epithelial membrane antigen (EMA) and CD99. In general, the Olig2-positive nuclei were only sparsely distributed in ependymomas; in contrast, they were very numerous in astrocytomas and oligodendrogliomas. Particularly in cases of glioblastoma or pilocytic astrocytoma that histologically mimicked ependymoma, the Olig2-positive nuclei were numerous as in conventional astrocytomas, which helped to differentiate them from ependymomas. The EMA-positive structures were helpful for the diagnosis of ependymoma, however, they were occasionally very modest and sparse on immunostained sections. A quantitative study showed that the Olig2-positive nuclei were much fewer in ependymomas than in astrocytomas and oligodendrogliomas. These results indicate that the Olig2-immunohistochemistry is useful and potentially more reliable than the EMA-immunohistochemistry for the diagnosis ofependymoma. CD99 is a cell surface antigen expressed in some tumors, most notably in Ewing's sarcomas. In our preliminary experiment, we noted the absence of CD99-immunoreactivity in a fraction of brain tumors with clear cell morphology, including oligodendroglioma, clear cell ependymoma, and pilocytic astrocytoma (the oligodendroglioma-like component). Thus, we investigated the expression of CD99 in an additional series of brain tumors with clear cell morphology, including oligoastrocytoma (7 cases), central neurocytoma (6), and dysembryoplastic neuroepithelial tumor (9). We found that the absence of CD99-immunoreactivity was dependent on clear cell morphology rather than on tumor entities. The CD99-immunohistochemistry is unique in that it is helpful for the diagnosis of clear cell brain tumors through the visualization of CD99-negative clear cells.