gms | German Medical Science

Objective: Eag1, a voltage-gated potassium channel is expressed in the brain, participating in the control of cell excitability. In addition, it has been implicated in malignant transformation and tumor progression in cancer cell lines and human malignancies. Eag1 function can be blocked in vitro and in vivo by monoclonal antibodies or drugs, such as tricyclic antidepressants. The few previous reports about the expression of Eag1 in gliomas have provided controversial results depending on the malignancy grade and tumor lineage.

Method: We have investigated 71 glioblastoma patients, who had undergone surgical resection followed by Stupp radio- and chemotherapy regime. 26/71 patients had been additionally treated with antidepressants because of endogenous depression (GliDep group), 45/71 patients (Gli group) had not. Sections of formalin-fixed, paraffin-embedded tumor samples were investigated by immunohistochemistry. A recombinant single chain, alkaline phosphatase fused antibody was used. The epitope for this antibody is located close to the putative pore region. The immunohistochemical localization of Eag1 was achieved using alkaline-phosphatase substrate and fast red counterstain. A semi-quantitative analysis was performed by microscopy using a four-grade score based on the HercepTest™ assay and validated by two independent observers. Statistical analysis was performed by using the t-test and Manova variance analysis (significance level, p<0.05).

Results: Eag1 staining was positive in 73% of the tumors in the GliDep group and in 80 % in the Gli group, respectively. In the Gli group patients displaying a low Eag1 expression (n=26) showed a longer survival time of 18.9 months than those with a high Eag1 expression (n=19, 11.1 months, p=0.07). Conversely, patients displaying a low Eag1 expression in the GliDep group (n=17) had a mean survival time of 11.7 months whereas patients with a high Eag1 expression (n=9) had a shorter mean survival time of 12.5 months (p=0.8).

Conclusions: Our results strongly suggest that patients with GBM scoring a low expression of the Eag1 potassium channel protein show a longer survival time than those with tumors expressing Eag1 at a high rate. Considering our own data, the relevance of drug-mediated blocking of Eag1 by tricyclic antidepressant appears to be less relevant than it is for brain metastasis, and requires further investigation encompassing alternative antibody epitopes.