Immunohistochemical expression of fibroblast growth factor (FGF)‐2 in epilepsy‐associated malformations of cortical development (MCDs)

Abstract

To elucidate the biological significance of dysplastic cells in malformations of cortical development, an immunohistochemical study was performed to investigate fibroblast growth factor-2 (FGF-2) expression in corticectomy specimens from epilepsy patients, including focal cortical dysplasia (FCD) with balloon cells (BCs) (n=4; age/sex=2M, 14F, 24M, 45M), tubers of tuberous sclerosis complex (TSC-tubers) (n=2; 1F, 3F), FCD without BCs (n=3; 23F, 23M, 25M), and gliotic lesions (n=3; 12M, 25M, 29M). The nucleus and/or cytoplasm of astrocytes in all cases examined were positive for FGF-2; however, FGF-2 immunoreactivity was not detected in oligodendroglial cells. In all dysplastic lesions, FGF-2 was detected in the astrocytic nuclei, and cytoplasm and/or nuclei of BCs. Dysplastic neurons (DNs) in FCD with BCs and TSC-tubers were variably positive for FGF-2 in the cytoplasm, but FGF-2 was not detected in the neurons of FCD without BCs. The number of FGF-2 immunoreactive cells (FGF-2-IR%) in FCD with BCs (46.0+/-4.1%) was higher than that in FCD without BCs (19.8+/-3.1%) and gliotic lesions (19.5+/-3.3%) with statistical significance (P<0.001). These results, together with previous reports showing FGF-2 expression in neuroblasts and glioblasts in human fetal brain, and mainly in astrocytes in adult brain, suggest that FGF-2 expression in MCDs reflects incomplete differentiation and maturation of dysplastic cells, and that FGF-2-IR% is associated with histological subtypes of MCD, reflecting the timing of insults underlying the pathogenesis of each disorder.