Expression of connexin 43 and connexin 32 gap-junction proteins in epilepsy-associated brain tumors and in the perilesional epileptic cortex

The expression of the gap-junction proteins connexin (CX) 43 and 32 was eva luated in surgical specimens of brain tumors and perilesional cortex from p atients with chronic medically intractable epilepsy. In human normal brain CX32 was expressed in neurons and oligodendrocytes. CX32 immunoreactivity ( IR) was observed in the neuronal component of glioneuronal tumors and in al l oligodendrogliomas, 50% of which showed strong labeling, independent of t he grade of differentiation. CX43, normally expressed in astrocytes, was al so detected in most of the human astrocytomas and in the astroglial compone nt of glioneuronal tumors. Whereas most of the low-grade gliomas (> 60%) sh owed strong membranous staining, most high-grade astrocytomas exhibited a r eduction of the typical plasma membrane CX43-IR and intracytoplasmic locali zation. Immunoblot analysis showed different CX43 isoforms in control corte x and in low-grade gliomas. However, only one single isoform (corresponding to the non-phosphorylated form of CX43) appeared to be present in most hig h-grade gliomas. Increased expression of CX43 protein was present in reacti ve astrocytes in the epileptic cortex surrounding low-grade tumors as compa red to control cortex, indicating the existence of a regulatory pathway inv olving CX43 in the reorganization of the astrocytic syncytium in regions un dergoing reactive gliosis. The high expression of connexin proteins in low- grade tumors and in the peritumoral reactive astrocytes suggests that they could contribute to tumor-related seizures.