High levels of connexin 43 mRNA in high grade astrocytomas. Study of 32 cases with in situ hybridization

Gap junctions are composed of a family of evolutionarily conserved integral plasma membrane proteins termed connexins. The aims of the research reported here were (1) to evaluate the Cx43 protein and mRNA of both low histological grade and high histological grade astrocyte tumors; (2) to evaluate if the immunohistochemistry of the Cx43 protein in astrocytomas could be correlated to histological grade, to proliferative activity (Ki67/Mib1-index) and to immunolabelling of the epidermal growth factor receptor (EGFR); (3) to evaluate if the reduction in levels of the Cx43 protein correlates with reduction in levels of the Cx43 mRNA. This study showed that the immunohistochemical labelling of Cx43 is reduced in grade III and grade IV. Decreased gap junction-mediated intercellular communication corresponds to decreased Cx43 and increased cellular proliferation rates, as measured by immunolabelling of the Ki67 nuclear antigen. This study demonstrated also the persistence in high grade astrocytomas of elevated levels of Cx43 mRNA. The reduced levels of Cx43 protein should not to be ascribed to a reduced genetic transcription, but to an alteration of the post-transcriptional mechanisms such as the regulation of its synthesis and/or the intracellular transport to membrane sites.