Usefulness of immunohistochemical expression analysis of metabolic-related molecules in differentiating between intracranial neoplastic and non-neoplastic lesions.

As the histologic features of reactive glial proliferation seen in many non-neoplastic lesions and of diffusely infiltrating gliomas overlap, tumor-specific diagnostic markers are needed. A mutation in isocitrate dehydrogenase 1 (IDH1), the enzyme involved in lipid metabolism and glucose sensing, has been identified in a variety of diffuse gliomas. The expression of fatty acid synthase (FAS), the enzyme responsible for the de novo synthesis of fatty acids, has been examined in several types of tumors including high-grade meningiomas, but not or less examined in normal tissues and benign tumors. We analyzed the expression of mutant IDH1 and FAS proteins in 10 non-neoplastic and 52 neoplastic lesions. Paraffin-embedded samples were immunostained with anti-IDH1R132H and -FAS antibodies. Staining of mutant IDH1 was positive in nine neoplastic lesions (3 diffuse astrocytomas, 2 anaplastic astrocytomas, and 1 oligodendroglioma, oligoastrocytoma, anaplastic oligodendroglioma, and glioblastoma); it was negative in all ten non-neoplastic lesions. Moreover, FAS expression was increased in glioblastomas (83.3%), anaplastic oligodendrogliomas and oligoastrocytomas (80%), and anaplastic astrocytomas (78.9%) compared with non-neoplastic lesions (20%). Immunostaining with mutant IDH1R132H-specific and FAS antibodies may be helpful to differentiate reactive from neoplastic cells in diffuse infiltrative or highly proliferative gliomas.