Vascular endothelial growth factor (VEGF) in leptomeningeal metastasis: diagnostic and prognostic value

Abstract

This study examined the diagnostic and prognostic value of vascular endothelial growth factor (VEGF) levels in the cerebrospinal fluid (CSF) of 39 patients with leptomeningeal metastasis (LM). Vascular endothelial growth factor levels at diagnosis were significantly higher in patients with LM (median 359 pg ml À1 ) than in patients with other neurological diseases (median o25 pg ml À1 ). The specificity of VEGF levels above 250 pg ml À1 for LM was high (98.3%), while the sensitivity was low (51.4%; 73% for VEGF values above 100 pg ml À1 ). In 49% of the LM patients, particularly with lymphoma or medulloblastoma, VEGF levels were below 250 pg ml À1 and thus in the range of VEGF levels in other neurological diseases. Vascular endothelial growth factor levels correlated significantly with CSF lactate and albumin. Vascular endothelial growth factor levels mirrored the clinical course with a marked reduction in response to therapy and an increase at relapse in some patients who had serial CSF samples available. Multivariate Cox regression analysis showed VEGF below 100 pg ml À1 (relative risk (RR) ¼ 4.24, P ¼ 0.0002) and age below 60 years (RR ¼ 2.5, P ¼ 0.004) to be associated with longer survival in LM. In conclusion, CSF VEGF levels in LM vary considerably. High VEGF levels have a very high specifity for LM and may help to establish the diagnosis. The role of VEGF as a predictor of outcome should be substantiated in prospective studies.

Contrast-Enhancing Meningeal Lesions Are Associated with Longer Survival in Breast Cancer-Related Leptomeningeal Metastasis

“…These nodular lesions are contrast enhancing, which is a sign for blood-CSF barrier disruption. There is also increasing evidence of neovascularization of such lesions, as vascular endothelial growth factor (VEGF) was detected in CSF of LM patients [11][12][13][14]. VEGF is a potent inducer of neovascularization but also of vascular permeability [15], therefore potentially contributing to the disruption of the blood-CSF barrier.…”

Clinical Presentation, Diagnosis, and Radiological Findings of Neoplastic Meningitis

“…87,88 Epidermal growth factor, vascular endothelial growth factor, and antithrombin 3 have been suggested as useful biomarkers, although antithrombin 3 has been evaluated in primary CNS lymphoma but not neoplastic meningitis. [89][90][91] Other markers such as creatinine kinase BB, tissue polypeptide antigen, and β-2 microglobulin are all indirect indicators of neoplastic meningitis and are still not sensitive enough to improve on findings seen on cytology. [91][92][93] The metabolome of CSF could be of use in detecting neoplastic meningitis.…”

“…[89][90][91] Other markers such as creatinine kinase BB, tissue polypeptide antigen, and β-2 microglobulin are all indirect indicators of neoplastic meningitis and are still not sensitive enough to improve on findings seen on cytology. [91][92][93] The metabolome of CSF could be of use in detecting neoplastic meningitis. Use of nuclear magnetic resonance spectroscopy based on variation seen in CSF metabolites is encouraging for the early detection of neoplastic meningitis in an animal model and now in humans.…”

CSF protein profiling using Multiplex Immuno-assay

“…A candidate protein in this respect is vascular endothelial growth factor (VEGF), as this angiogenic protein was found to be highly elevated in the CSF of LM patients as compared with patients with infectious meningitis [11,19,22]. Furthermore, dedifferentiation markers like CEA (or CA 15-3), although showing a low sensitivity for LM when measured as a single biomarker (31%), may contribute to the specificity of a CSF protein profile in LM patients [25].…”