Expression of the LGI1 gene product in astrocytic gliomas: downregulation with malignant progression

Loss of heterozygosity in the long arm of chromosome 10q is a frequent event in gliomas. It may involve the LGI1/epitempin gene, which is located in chromosomal region 10q23 approximately 24 and has been proposed to encode a tumor suppressor inactivated in the progression of brain tumors. Nevertheless, so far no data are available demonstrating that the reduced expression of the LGI1 transcript in high-grade astrocytic tumors indeed results in a decreased level of LGI1 protein in the tumor cells. Thus, the aim of the present study was to analyze the expression of the LGI1 protein in a series (ten of each) of pilocytic astrocytomas, astrocytomas [World Health Organization (WHO) grade II], anaplastic astrocytomas (WHO grade III), and glioblastoma multiforme (WHO grade IV). Immunohistochemistry demonstrated a strong expression of the LGI1 protein in normal brain tissue as well as in the majority of pilocytic astrocytomas and astrocytomas (WHO grade II). In anaplastic astrocytomas, the number of tumor cells expressing LGI1 decreased, while LGI1 expression was completely absent from the glioblastomas of this series. This highly significant reduction of LGI1 protein expression in the progression of astrocytic brain tumors lends further support to the hypothesized function of LGI1 as a type-II tumor suppressor gene in glioma pathogenesis.