CSF levels of growth factors and plasminogen activators in leptomeningeal metastases

Objective: To investigate the diagnostic value of transforming growth factor β₁ (TGFβ₁), vascular endothelial growth factor (VEGF), urokinase-type plasminogen activator (uPA), and tissue-type plasminogen activator (tPA) in CSF for leptomeningeal metastasis (LM). Methods: The authors measured concentrations of biomarkers by ELISA in matched samples of CSF and serum, collected from 132 patients with a solid malignancy with LM (n = 19) and without LM (n = 54) and patients with viral (n = 16) and bacterial (n = 16) meningitis and a variety of nonmalignant, noninfectious neurologic disorders (n = 27). Indexes of the biomarkers (CSF/serum value relative to CSF/serum albumin ratios) were calculated to correct for the serum contribution to the CSF marker concentration. Results: CSF VEGF concentration was significantly higher in LM than in all other groups. VEGF indexes were also higher, although not significant. In contrast, the tPA index was significantly decreased in LM compared with all other groups. The combination of the VEGF and tPA indexes resulted in a sensitivity of 100% for LM and a specificity of 73% for the patient group with a primary tumor but without LM. Conclusion: Patients with leptomeningeal metastasis have high vascular endothelial growth factor (VEGF) indexes and low tissue-type plasminogen activator (tPA) indexes. As cytologic examination of CSF lacks 100% sensitivity for the diagnosis of leptomeningeal metastasis (LM), the combination VEGF and tPA index analysis may be of additional value in the diagnostic workup of patients suspected of having LM.