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). MATERIALS AND 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.
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 cancerpatients being evaluated for neoplastic meningitis (NM). MATERIALS AND 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 melanomapatients at risk for NM, is warranted.
Authors: Xin Hong; Feng Jiang; Steven N Kalkanis; Zheng Gang Zhang; Xue-Peng Zhang; Ana C DeCarvalho; Mark Katakowski; Kevin Bobbitt; Tom Mikkelsen; Michael Chopp Journal: Cancer Lett Date: 2005-06-20 Impact factor: 8.679
Authors: Roderick J Phillips; Marie D Burdick; Marin Lutz; John A Belperio; Michael P Keane; Robert M Strieter Journal: Am J Respir Crit Care Med Date: 2003-03-05 Impact factor: 21.405
Authors: B van de Langerijt; J M Gijtenbeek; H P M de Reus; F C G J Sweep; A Geurts-Moespot; J C M Hendriks; A C Kappelle; M M Verbeek Journal: Neurology Date: 2006-07-11 Impact factor: 9.910
Authors: G Stockhammer; W Poewe; S Burgstaller; F Deisenhammer; A Muigg; S Kiechl; E Schmutzhard; H Maier; S Felber; P Schumacher; E Gunsilius; G Gastl Journal: Neurology Date: 2000-04-25 Impact factor: 9.910
Authors: O Watanabe; I Maruyama; K Arimura; I Kitajima; H Arimura; M Hanatani; K Matsuo; T Arisato; M Osame Journal: Muscle Nerve Date: 1998-11 Impact factor: 3.217
Authors: S T Rosen; J Aisner; R W Makuch; M J Matthews; D C Ihde; M Whitacre; E J Glatstein; P H Wiernik; A S Lichter; P A Bunn Journal: Medicine (Baltimore) Date: 1982-01 Impact factor: 1.889
Authors: Lindsay Angus; John W M Martens; Martin J van den Bent; Peter A E Sillevis Smitt; Stefan Sleijfer; Agnes Jager Journal: Neuro Oncol Date: 2019-03-18 Impact factor: 12.300
Authors: Pavel Gromov; Irina Gromova; Jakob Bunkenborg; Teresa Cabezon; José M A Moreira; Vera Timmermans-Wielenga; Peter Roepstorff; Fritz Rank; Julio E Celis Journal: Mol Oncol Date: 2009-11-23 Impact factor: 6.603
Authors: Emilie Le Rhun; Andrew Kramar; Sophie Salingue; Marie Girot; Isabelle Rodrigues; Audrey Mailliez; Fahed Zairi; Edgar Bakhache; Yves Marie Robin; Sophie Taillibert; François Dubois; Jacques Bonneterre; Marc C Chamberlain Journal: J Neurooncol Date: 2014-01-28 Impact factor: 4.130
Authors: Dmitry A Nedosekin; Mazen A Juratli; Mustafa Sarimollaoglu; Christopher L Moore; Nancy J Rusch; Mark S Smeltzer; Vladimir P Zharov; Ekaterina I Galanzha Journal: J Biophotonics Date: 2013-05-16 Impact factor: 3.207