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 progression in a variety of human malignancies and in cancer cell lines. In this analysis, we aimed to compare the expression of Eag1 in brain metastases and corresponding primary carcinomas.

Method: 75 patients (39 males, 36 females, median age: 60.7 y.) with brain metastases from different cancers, who had undergone surgery and adjuvant radiotherapy were analyzed. Tumor tissue from their corresponding primary carcinoma was available in 30 cases. Formalin-fixed, paraffin-embedded tumor samples were investigated by immunohistochemistry. A recombinant single chain, alkaline phosphatase fused antibody with an epitope located close to the putative pore region was used. The immunohistochemical Eag1 localization was achieved using alkaline-phosphatase substrate and fast red counterstain. A semi-quantitative microscopic analysis was performed using a four-grade score based on the HercepTest^TM assay and validated by two independent observers. Statistical analysis was performed by using the t-test and the Wilcoxon test (significance level, p<0.05).

Results: Eag1 staining was positive in 88% of the brain metastases and in 30% of the primary carcinomas. By semiquantitative densitometric evaluation of matched-paired samples, we found that the expression of Eag1 was significantly higher in brain metastases in 54% of the cases, as compared to the corresponding carcinoma, p=0.035). Moreover, the expression of Eag1 in brain metastasis was lower than in their matched carcinomas in 16% of the patients and remained unchanged in 30%. Patients displaying a high Eag1 expression in brain metastases (n=18) showed a shorter mean survival time of 7.2 months, whereas patients with a low Eag1 expression (n=12) had a mean survival time of 13.5 months (p=0.05).

Conclusions: Our analyses show that in the process of metastasizing to the brain, a significant increase of the expression of Eag1 frequently occurred. Furthermore, a high expression of Eag1 in brain metastasis was associated with a poorer patient prognosis. Our data strongly suggest that up-regulation of the Eag1 gene in primary carcinomas might be associated with higher risk of metastasis to the brain.