N-cadherin, beta-catenin and connexin 43 expression in astrocytic tumours of various grades.

Abstract

Astrocytic tumors are the most common primary brain tumors, but little is known about their etiology and prognostic factors. N-cadherin and beta-catenin are adhesive proteins, and are often overexpressed in many types of cancers, including breast or colorectal cancer, resulting in better prognosis. Connexin 43 is a gap junction protein involved in cell-cell signaling pathway taking part in the process of carcinogenesis. The aim of the study was to evaluate N-cadherin, beta-catenin and connexin 43 expression in astrocytic tumors of various grades. We examined 131 cases of astrocytic tumors, including 26 cases of diffuse astrocytoma (group I), 44 anaplasic astrocytomas (group II) and 61 glioblastoma cases (group III)--primary and secondary. To evaluate N-cadherin, beta-catenin and connexin 43 expression, we used immunohistochemical reaction with specific antibodies (Santa Cruz Biotechnology). The obtained results were correlated with clinical and morphological features. Beta-catenin expression was observed in 69.3% of diffuse astrocytomas, 75% of anaplastic astrocytomas, and 82% of glioblastoma cases. N-cadherin expression was observed in 92.3% of diffuse astrocytomas, 90.1% of anaplastic astyrocytomas, and in all glioblastoma cases. Connexin 43 was observed in 76.9% of diffuse astrocytomas, and in all cases of anaplastic astrocytomas and glioblastomas. Beta-catenin expression was significant within the nucleus of neoplastic cells in groups I and II. In group III, staining was observed only in the cellular membranes. N-cadherin and connexin 43 expression was observed only in the cells' membranes. In glioblastomas, both primary and secondary, all protein expression was significant within the cells surrounding the necroses and blood vessels and weak or absent in the tumor's margins. Our study shows that beta-catenin nuclear expression in group of diffuse astrocytomas and anaplastic astrocytomas is evidence for transcriptional function of beta-catenin in those groups. Strong N-cadherin and connexin 43 expression in those groups may be evidence for their role in tumor formation and progression. However, in glioblastomas a very important role of all examined proteins is generating intracellular connections to facilitate the escape of tumor cells from the effects of hypoxia or their accumulation around the blood vessels rather than tumor invasion into the brain parenchyma.