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BMC Cancer ; 15: 839, 2015 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-26530050

RESUMO

BACKGROUND: Kv10.1, a voltage-gated potassium channel only detected in the healthy brain, was found to be aberrantly expressed in extracerebral cancers. Investigations of Kv10.1 in brain metastasis and glioblastoma multiforme (GBM) are lacking. METHODS: We analyzed the expression of Kv10.1 by immunohistochemistry in these brain tumors (75 metastasis from different primary tumors, 71 GBM patients) and the influence of a therapy with tricyclic antidepressants (which are Kv10.1 blockers) on survival. We also investigated Kv10.1 expression in the corresponding primary carcinomas of metastases patients. RESULTS: We observed positive Kv10.1 expression in 85.3 % of the brain metastases and in 77.5 % of GBMs. Patients with brain metastases, showing low Kv10.1 expression, had a significantly longer overall survival compared to those patients with high Kv10.1 expression. Metastases patients displaying low Kv10.1 expression and also receiving tricyclic antidepressants showed a significantly longer median overall survival as compared to untreated patients. CONCLUSIONS: Our data show that Kv10.1 is not only highly expressed in malignant tumors outside CNS, but also in the most frequent cerebral cancer entities, metastasis and GBM, which remain incurable in spite of aggressive multimodal therapies. Our results extend the correlation between dismal prognosis and Kv10.1 expression to patients with brain metastases or GBMs and, moreover, they strongly suggest a role of tricyclic antidepressants for personalized therapy of brain malignancies.


Assuntos
Neoplasias Encefálicas/genética , Canais de Potássio Éter-A-Go-Go/biossíntese , Glioblastoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Intervalo Livre de Doença , Canais de Potássio Éter-A-Go-Go/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
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