title: Biomarkers of disease: cerebrospinal fluid vascular endothelial growth factor (VEGF) and stromal cell derived factor (SDF)-1 levels in patients with neoplastic meningitis (NM) due to breast cancer, lung cancer and melanoma.
abstract: BACKGROUND
  Breast cancer, lung cancer and melanoma metastasize to the meninges in 5-15% of patients. The identification of specific biomarkers of disease may allow for earlier diagnosis and treatment. Preclinical evidence suggests the possible relevance of SDF-1 and VEGF in the homing and neoangiogenesis of metastases. We chose to measure these molecules in the cerebrospinal fluid (CSF) of melanoma, breast, and lung cancer patients being evaluated for neoplastic meningitis (NM).
  
  
  METHODS
  We collected CSF from patients with these cancers who were being evaluated for possible NM. CSF was assayed for SDF-1 and VEGF levels using Enzyme-linked Immunosorbent Assay (ELISA) assays.
  
  
  RESULTS
  CSF samples from 89 patients met criteria for analysis, including 41 with breast cancer, 35 with lung cancer and 13 with melanoma. Twenty-five percent (22/89) of all samples were positive for malignant cells; 8/41 (20%) from breast cancer, 10/35 (29%) from lung cancer and 4/13 (31%) from melanoma. CSF VEGF levels were available from 83 patients, and were elevated (>20 pg/ml) in 15/22 (68%) of patients with positive CSF cytology and normal (<20 pg/ml) in 59/61 (97%) of patients with negative CSF cytology. The two patients with negative CSF cytology who also had elevated CSF VEGF levels had MRI evidence of NM. CSF SDF-1 levels were available from 81 patients, and were elevated (>950 pg/ml) in 11/18 (61%) of patients with positive CSF cytology and normal (<950 pg/ml) in 57/63 (90%) of patients with negative CSF cytology.
  
  
  CONCLUSIONS
  Elevated CSF levels of VEGF are sensitive and highly specific for the diagnosis of NM from breast cancer, lung cancer and melanoma, and may serve as a useful biomarker of NM in high risk patients. CSF SDF-1 levels add little to the diagnostic information provided by CSF VEGF. Evaluation of CSF VEGF levels as a trigger for early treatment in high risk breast cancer, lung cancer and melanoma patients at risk for NM, is warranted.
authors.affiliation: Departments of Neuro-Oncology, The Brain Tumor Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. mgroves@mdanderson.org.
authors.forename: Morris D
authors.initials: MD
authors.lastname: Groves
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Hess
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Puduvalli
authors.forename: Howard
authors.initials: H
authors.lastname: Colman
authors.forename: Charles A
authors.initials: CA
authors.lastname: Conrad
authors.forename: Mark R
authors.initials: MR
authors.lastname: Gilbert
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Weinberg
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
authors.forename: W K Alfred
authors.initials: WK
authors.lastname: Yung
authors.forename: Ta-Jen
authors.initials: TJ
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000134:cerebrospinal fluid; D001943:Breast Neoplasms / Q000134:cerebrospinal fluid* / Q000150:complications / Q000473:pathology; D054377:Chemokine CXCL12 / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000134:cerebrospinal fluid* / Q000150:complications / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000134:cerebrospinal fluid* / Q000150:complications / Q000473:pathology; D008581:Meningitis / Q000134:cerebrospinal fluid* / Q000209:etiology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000134:cerebrospinal fluid; D009367:Neoplasm Staging; D011379:Prognosis; D012680:Sensitivity and Specificity; D042461:Vascular Endothelial Growth Factor A / Q000134:cerebrospinal fluid*
chemical_list: D014408:Biomarkers, Tumor; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A