The majority of brain metastases originate from lung cancer, breast cancer and malignant melanoma.,In order to reach the brain, parenchyma metastatic cells have to transmigrate through the endothelial cell layer of brain capillaries, which forms the morphological basis of the blood-brain barrier (BBB).,The BBB has a dual role in brain metastasis formation: it forms a tight barrier protecting the central nervous system from entering cancer cells, but it is also actively involved in protecting metastatic cells during extravasation and proliferation in the brain.,The mechanisms of interaction of cancer cells and cerebral endothelial cells are largely uncharacterized.,Here, we provide a comprehensive review on our current knowledge about the role of junctional and adhesion molecules, soluble factors, proteolytic enzymes and signaling pathways mediating the attachment of tumor cells to brain endothelial cells and the transendothelial migration of metastatic cells.,Since brain metastases represent a great therapeutic challenge, it is indispensable to understand the mechanisms of the interaction of tumor cells with the BBB in order to find targets of prevention of brain metastasis formation.
This retrospective study aimed to identify prognostic factors in patients with brain metastases from cutaneous melanoma.,In all, 265 patients under regular screening according to valid national surveillance guidelines were included in the study.,Kaplan-Meier analyses were performed to estimate and to compare overall survival.,Cox modeling was used to identify independent determinants of the overall survival, which were used in explorative classification and regression tree analysis to define meaningful prognostic groups.,In total, 55.5% of our patients presented with two or less brain metastases, 82.6% had concurrent extracranial metastasis and 64% were asymptomatic and diagnosed during surveillance scans.,In all, 36.7% were candidates for local treatment (neurosurgery or stereotactic radiosurgery (SRS)).,The median overall survival of the entire collective was 5.0 months (95% confidence interval: 4.3-5.7).,Favourable independent prognostic factors were: normal pre-treatment level of serum lactate dehydrogenase (P<0.001), administered therapy (neurosurgery or SRS vs other, P=0.002), number of brain metastases (single vs multiple, P=0.032) and presence of bone metastasis (false vs true, P=0.044).,Three prognostic groups with significantly different overall survival were identified.,Candidates for local treatment (group I) had the longer median survival (9 months).,Remaining patients could be further classified in two groups on the basis of serum lactate dehydrogenase.,Applied treatment and serum lactate dehydrogenase levels were independent predictors of survival of patients with brain metastases from cutaneous melanoma.,Patients receiving local therapy have overall survival comparable with general stage IV melanoma patients.