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- Title
VEGF (Vascular Endothelial Growth Factor) in cerebrospinal fluid: a new tumour marker for carcinomatous meningitis.
- Authors
Stockhammer G; Jäger IM; Ruffini I; Deisenhammer F; Schumacher P; Gunsilius E; Schulze E; Muigg A
- Abstract
Carcinomatous meningitis (CM) is a devastating neurological complication of cancer occurring in 3 - 8% of all cancer patients, resulting in neurological morbidity and a high mortality. The detection of tumour cells in the cerebrospinal fluid (CSF) remains the gold standard for the definite diagnosis of CM. However, in the absence of positive CSF cytology, its diagnosis may be difficult. In such instances, tumour markers have been proposed as helpful adjuncts in the diagnosis and management of tumour spread to the leptomeninges. During the past two decades, a number of biochemical markers have been evaluated as a means of detecting CM. Unfortunately, currently available biochemical markers are known for their low sensitivity when assisting in the diagnosis of CM. Thus, more reliable tools are needed for the diagnosis of CM and for monitoring treatment response.The aim of this article is to summarize our experience trying to define the role of CSF-VEGF (vascular endothelial growth factor) as a new tumour marker for the diagnosis and follow-up of patients with CM. Under the hypothesis that spread of malignancy to the leptomeninges may be reflected by VEGF levels in the CSF, we determined the value of VEGF in CSF as a marker for carcinomatous meningitis. The concentration of VEGF was measured by means of ELISA in matched samples of CSF and serum collected from 162 patients, including solid tumours with CM (n = 11) or brain metastases without concomitant CM (n = 12), paraneoplastic neurological syndromes (n = 4), viral (n = 15) and bacterial (n = 20) meningitis, and a variety of non-neoplastic and noninfectious neurological diseases (n = 100). High VEGF levels (range 745.1 - 18,791; median 6794.8 pg/mL) were found in CSF of all patients with CM, while VEGF levels in matched sera were comparable to other disease groups. Median VEGF concentration in CSF from patients with acute bacterial meningitis was 38.6 pg/mL (range > 25 - 633.1 pg/mL), with only nine of these 17 patients showing detectable VEGF levels in CSF. Using CSF/serum albumin ratios, a VEGF index was calculated to estimate the proportion of intrathecally produced VEGF. The VEGF indices in patients with bacterial meningitis were significantly lower than in tumour patients with CM (> 22.8 vs. < 62.3, respectively), suggesting that the proportion of intrathecally produced VEGF is much higher in patients with CM as compared to patients with bacterial meningitis. Patients without neoplastic or infectious neurological disorders, viral meningitis or neurological autoimmune disorders consistently showed VEGF levels in CSF below the assay detection limit of 25 pg/mL. Immunohistochemical staining for VEGF was performed in a brain metastasis from a mammary carcinoma associated with CM. Immunohistochemistry revealed strong cytoplasmic VEGF staining of the tumour cells. In addition, in 10 patients VEGF levels in CSF and serum were monitored during antineoplastic treatment and correlated with clinical course, imaging studies and CSF cytology. CSF-VEGF levels correlated well with clinical course, therapeutic response and the presence of malignant cells in the CSF. In some patients, CSF-VEGF was an earlier predictor of tumour relapse compared to CSF cytology.In conclusion, in patients with CM, significant amounts of VEGF are released into the CSF. Thus, VEGF in CSF is a useful biological marker for both the diagnosis and evaluation of treatment response in CM. Compared to CSF cytology, CSF-VEGF may give additional information and may represent an earlier predictor of tumour relapse. The ELISA assay represents an easy and sen-sitive technique for determining VEGF concentrations and could be easily implemented in routine CSF studies.
- Publication
Journal of Laboratory Medicine / Laboratoriums Medizin, 2003, Vol 27, Issue 9/10, p329
- ISSN
0342-3026
- Publication type
Journal Article