Indicators of the fibrinolytic system in the blood and cerebrospinal fluid of patients with metastatic brain lesions

Introduction. Brain metastases – the most common type of intracranial secondary neoplasms in adults – are characterized by high mortality and are the main cause of death in almost 1/5 of all oncological patients. For neoplasms of various locations, it was shown that fibrinolytic system plays a large role in malignant cell invasion.

Aim. To evaluate the level and activity of the main components of the plasminogen activation system in blood and cerebrospinal fluid (CSF) of patients with brain metastases.

Materials and methods. Using enzyme immunoassay, the main parameters of fibrinolytic system functioning were determined in plasma of 38 patients of both sexes aged 59.9 ± 8.9 years with morphologically verified primary pathological tumor and magnetic resonance imaging-confirmed intracranial metastatic lesions without dislocation syndrome. The level and activity of tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1) and urokinase receptor (uPAR) were measured. The results were compared to data from 18 individuals without oncological pathology (donor group). The levels and activity of uPA and tPA, as well as PAI-1 inhibitor and uPAR were also evaluated in CSF of 16 patients with brain metastases and 14 patients with benign brain tumors. Statistical data processing was performed using the Statistica 10.0 software.

Results. In plasma of patients with brain metastases, tPA activity was increased 2.1-fold while its level was decreased 3.6-fold which increased their ratio 10-fold (p £0.0002). uPA activity did not change but its level, as well as uPAR level, activity and level of PAI-1 inhibitor and tPA and uPA were decreased. In CSF of patients with brain metastases, the levels of urokinase system components were lower compared to CSF of patients with benign brain tumors. For benign tumors, PAI-1 inhibitor level was 3.5 times higher than for brain metastases (p = 0.0000), while there were no differences in tPA parameters in CSF.

Conclusion. In blood of patients with brain metastases, only tPA activation was observed. The results allow to propose that in patients with brain metastases, functional activity of urokinase system is not elevated in blood and, supposedly, in CSF in contrast to patients with primary malignant tumors of some locations.

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