Vascular endothelial growth factor in CSF - A biological marker for carcinomatous meningitis

Objective: To determine the value of vascular endothelial growth factor (VE GF) in CSF as a marker for carcinomatous meningitis (CM). Methods: The conc entration of VEGF was measured by ELISA in matched samples of CSF and serum collected from 162 patients. These included patients with solid tumors wit h CM (n = 11) or brain metastases without concomitant CM (n = 12), paraneop lastic neurologic syndromes (n = 4), viral (n = 15) and bacterial (n = 20) meningitis, and a variety of non-neoplastic and noninfectious neurologic di seases (n = 100). Using CSF/serum albumin ratios, the VEGF index was calcul ated to estimate the proportion of intrathecally produced VEGF. Immunohisto chemical staining for VEGF was performed in a brain metastasis from a mamma ry carcinoma associated with CM. Results: High VEGF levels (median 6,794.8 pg/mL) were found in CSF of all patients with CM, whereas VEGF levels in ma tched sera were comparable to other disease groups. In patients with CM, th e concentration of VEGF in CSF decreased significantly following antineopla stic treatment. In CSF samples from patients with brain metastases without concomitant CM, VEGF was not detectable. Median VEGF concentration in CSF f rom patients with acute bacterial meningitis was 38.6 pg/mL, with only 9 of these 17 patients showing detectable VEGF levels in CSF. The VEGF indices in patients with bacterial meningitis were significantly lower than in tumo r patients with CM (<22.8 versus >62.3), suggesting that the proportion of intrathecally produced VEGF is much higher in patients with CM as compared with patients with bacterial meningitis. Patients without neoplastic or inf ectious neurologic disorders consistently showed VEGF levels in CSF below t he assay detection limit of 25 pg/mL. Immunohistochemistry revealed strong cytoplasmic staining for VEGF in a metastatic lesion from breast cancer inf iltrating the meninges. Conclusion: In patients with carcinomatous meningit is, significant amounts of VEGF are released into CSF. This study yields pr eliminary evidence that VEGF in CSF may be a useful biologic marker for bot h the diagnosis and evaluation of treatment response in carcinomatous menin gitis.