血管内皮生长因子在卵巢上皮性癌中的表达

目的 探讨血管内皮生长因子（ｖｅｓｃｕｌａｒ ｅｎｄｏｔｈｅｌｉａｌ ｇｒｏｗｔｈ ｆａｃｔｏｒ,ＶＥＧＦ）在血管生成及其在卵巢癌发展中的作用。方法 用免疫组织化学方法检测ＶＥＧＦ在７９例人卵巢上皮性癌组织中的表达,并标记肿瘤内血管,分析ＶＥＧＦ与瘤内微血管密度（ｍｉｃｒｏｖｅｓｓｅｌ ｄｅｎｓｉｔｙ,ＭＶＤ）及其与组织学分类、临床分期、腹水、淋巴结转移、预后的关系。结果 在７９例卵巢上皮性癌中５     

Correlations of oral tongue cancer invasion with matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) expression

BACKGROUND AND OBJECTIVES: In oral tongue cancer, the degree of tumor invasion has a significant effect on the prognosis. We hypothesized that the destruction of extracellular matrix and neovascularization are related to tumor infiltration mechanism. By studying the tissues of early stage oral tongue cancer patients, we are intending to clarify the invasion-related factors. MATERIALS AND METHODS: To demonstrate the invasion process in early T-stage oral tongue cancer, the expressions of extracellular matrix destruction-related molecules (MMP-2, MMP-9) and neovascularization-related molecule (VEGF) were observed by immunohistochemical study. Also, staining of CD31 was done for quantification of neovascularization. We analyzed relationship between expression of each substances and tumor invasion depth, tumor free survival rates, and cervical lymph node metastasis rate. RESULTS: The expression rates of MMP-2, MMP-9, VEGF in 38 early oral cancer patients were 52.6%, 78.9%, and 52.6%, respectively. Significant correlation was found between the VEGF expression and microvessel density showed by CD31 immunohistochemical staining (P < 0.001). VEGF expressions were significantly related with tumor invasion depth (P = 0.002). The tumor-free survival rate of those patients with VEGF-positive tumors was significantly poorer than in those with VEGF-negative tumors (P = 0.019). CONCLUSIONS: These results indicate that VEGF is a useful marker for predicting the tumor invasion in patients with early tongue cancer.     

Clinical implications of expression of vascular endothelial growth factor in metastatic lesions of ovarian cancers

Vascular endothelial growth factor (VEGF) has been identified as an important factor for tumour angiogenesis, which is essential for the growth, invasion and metastasis of solid tumours. Significantly increased VEGF level from the primary tumour to the metastatic lesion of ovarian cancers was found in 8 of 30 cases. The 24-month survival rate of the patients with significantly increased VEGF level was extremely poor (0/8 = 0%) in comparison with that of patients with no change in the level (15/22 = 68%) from the primary tumour to the metastatic lesion. This indicates that VEGF may contribute to the advancement of metastatic lesions, and that VEGF level in metastatic lesions may be a prognostic indicator.     

Vascular endothelial growth factor staining and elevated INR in advanced epithelial ovarian carcinoma

BACKGROUND: The purpose of this study was to determine whether vascular endothelial growth factor (VEGF) expression in tumors correlates with the incidence of an elevated prothrombin time (PT), specifically an international normalized ratio (INR) > or = 1.4, in patients undergoing primary surgical cytoreduction for ovarian cancer. METHODS: INRs were obtained on all patients perioperatively. VEGF expression was determined by immunostaining of tumor specimens using published protocols. RESULTS: One hundred patients underwent surgical cytoreduction. Sixty-seven percent of patients had postoperative INR of 1.4 or greater. INRs of greater than or equal to 1.8 were found in 5% of patients. INR elevation was independent of mean estimated blood loss (EBL) with the EBL in the patients with INRs > or = 1.4 not significantly different than the EBL in the patients with INRs < 1.4 (660 ml vs. 530 ml, P = 0.09). There was a significant correlation between elevated INR and tumor VEGF immunostaining (P < 0.005). All but one patient with an elevated INR had positive VEGF staining. CONCLUSIONS: In conclusion, development of an elevated INR (INR > or = 1.4) is common in patients undergoing primary surgical cytoreduction. Positive tumor VEGF staining is very common in patients having a postoperative coagulopathy.     

Clinical significance of heparin-binding epidermal growth factor-like growth factor in peritoneal fluid of ovarian cancer

Epidermal growth factor receptor (EGFR) has been implicated in tumour growth and extension of ovarian cancer. Peritoneal fluid in ovarian cancer patients contains various growth factors that can promote tumour growth and extension. In order to investigate the clinical significance of EGFR ligands as activating factors of ovarian cancer, we examined the cell proliferation-promoting activity and the level of EGFR ligands in peritoneal fluid obtained from 99 patients. Proliferation-promoting activity in peritoneal fluid from 63 ovarian cancer patients (OVCA) was much higher than peritoneal fluid from 18 ovarian cyst patients (OVC) and 18 normal ovary patients (NO), and the activity was suppressed only by antibodies against EGFR or heparin-binding epidermal growth factor (HB-EGF). A large difference was observed in the level of EGFR ligands between HB-EGF and TGF-alpha or amphiregulin. The concentration of HB-EGF in OVCA significantly increased compared to that in OVC or NO (P<0.01). No significant difference in the concentration of TGF-alpha and amphiregulin was found between the OVCA and NO or OVC groups. In peritoneal fluid, HB-EGF is sufficiently elevated to activate cancer cells even at an early stage of OVCA. These results suggested that HB-EGF in peritoneal fluid might play a key role in cell survival and in the proliferation of OVCA.     

Vascular endothelial growth factor (VEGF) levels and mutation of the BRCA1 gene in breast cancer patients

The aim of the study was to compare VEGF serum levels in breast cancer patients with and without BRCA1 gene mutation. We enrolled 80 patients, 22 premenopausal and 58 postmenopausal. We found statistically significant lower levels of VEGF in patients with BRCA1 gene mutation as compared with breast cancer patients without this mutation.     

Co-expression of vascular endothelial growth factor (VEGF) and its receptors (flk-1 and flt-1) in hormone-induced mammary cancer in the Noble rat

Vascular endothelial growth factor (VEGF) is recognized to play a predominant role in breast cancer prognosis. The action of VEGF is mediated by two high-affinity receptors with ligand-stimulated tyrosine kinase activity: VEGFR-1/flt-1 and VEGFR-2/flk-1, which are expressed mainly in vascular endothelial cells. To the best of our knowledge, no previous studies on the expression of these receptors in breast cancer cells has been made. We have established a new animal model for breast cancer, using a combination of 17beta-oestradiol and testosterone as 'carcinogens'. Taking advantage of the animal model, we have demonstrated that mammary cancer cells expressed not only high levels of VEGF but also, surprisingly, its receptors (fit-1 and flk-1) in mammary cancer cells. Intense reactivities to VEGF, flt-1 and flk-1 were observed in mammary cancer cells, especially in invasive mammary carcinoma. Western blot analysis confirmed the increase in flk-1 and flt-1 proteins in induced mammary cancers. Based on these observations, we hypothesize that in mammary cancer, VEGF regulates, in addition to endothelial proliferation and angiogenesis, also growth of cancer cells by an autocrine mechanism mediated through its receptors. To further verify this hypothesis, we investigated the correlation between cellular proliferation and the expression of VEGF, flt-1 and flk-1. Using double-labelling immunocytochemistry, we have shown a correlation between high VEGF activity and Ki-67 expression. The Ki-67 indices in the areas of strong and weak VEGF reactivities were 58.3% and 3.7% respectively. Similarly, there was also a correlation of strong flk-1 and Ki-67 reactivity. The Ki-67 indices for areas of strong and weak flk-1 reactivities were 53.9% and 3.1% respectively. On the other hand, there was a reverse correlation between fit-1 and Ki-67 activities. These results indicate that overexpression of VEGF and flk-1 is correlated with high Ki-67 index. The data, therefore, suggest that VEGF may act as an autocrine growth factor for mammary cancer cells in vivo and this autocrine regulatory role may be mediated through flk-1. The present study is the first report showing that VEGF may act as a growth stimulator for mammary cancer cells.     

Ribozyme approach to downregulate vascular endothelial growth factor (VEGF) 189 expression in non-small cell lung cancer (NSCLC)

The aim of this study was to further clarify the role of the cell-associated isoform of vascular endothelial growth factor (VEGF189) on tumour growth and vascularity. Five isoforms of VEGF have been identified with different biological activities. VEGF121, VEGF145, VEGF165, VEGF189, VEGF206 are generated by alternative splicing. We used a hammerhead-type ribozyme (V189Rz) to suppress VEGF189 mRNA. The V189Rz specifically cleaved exon 6 of VEGF189 mRNA, but showed no activity against the VEGF121 or VEGF165 isoforms. The V189Rz was introduced into the human non-small cell lung cancer (NSCLC) cell line (OZ-6/VR). The expression level of VEGF189 mRNA was decreased in the OZ-6/VR cells, while VEGF121 and 165 expression was unaltered. The OZ-6/VR cells xenotransplanted into nude mice showed markedly reduced vascularisation and growth, whereas the cell line did not show any decreased growth under tissue culture conditions. The OZ-6/VR cells (1×10⁵ cells/mouse) formed no tumours, whereas the parental OZ-6 cells formed large tumours within 8 weeks. The specific suppression of VEGF189 by the ribozyme decreased vascularity and xenotransplantability of the lung cancer cell line. Thus, the cell-associated isoform of VEGF, VEGF189, might have a key role in stromal vascularisation and the growth of NSCLC xenografts in vivo.     

Serum vascular endothelial growth factor (VEGF) levels correlate with tumor VEGF and p53 overexpression in endocrine positive primary breast cancer

Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis, associated with unfavorable clinical characteristics in breast cancer. The aim of this study was to evaluate different angiogenic markers in endocrine-positive breast cancer patients. The authors analyzed serum and tumor samples from 71 patients with endocrine-positive operable primary breast cancer to determine the expression and the possible relationship between circulating serum VEGF levels, tumor VEGF expression, microvessel density (MVD), and other immunohistochemical parameters. Basal VEGF serum levels were significantly higher in breast cancer patients than in healthy controls. A significant correlation was observed between basal VEGF serum concentrations, microvessel density (p = 0.01) and p53 status (p = 0.004). Intratumoral VEGF expression was significantly associated with neoplastic embolization (p = 0.041) and circulating VEGF levels (p = 0.047). The results confirm that in primary endocrine-positive breast cancer serum VEGF levels are elevated and show a positive relationship with tumor VEGF and p53 overexpression.     

Effect of paclitaxel on vascular endothelial growth factor (VEGF) and interleukin (IL)-8 in serum of patients with recurrent ovarian cancer: a comparison of weekly vs triweekly regimens

Antiangiogenic scheduling of cancer chemotherapeutics has been increasingly recognized to be a potential application of the paclitaxel in cancer therapy. The purpose of this study is to confirm antiangiogenic effects of weekly low-dose paclitaxel in recurrent ovarian carcinoma. Measurements of serum vascular endothelial cell growth factor (VEGF) and interleukin (IL)-8 were performed using enzyme-linked immunosorbent assay (ELISA) kits. Serum was collected with written informed consents. Serum levels of VEGF and IL-8 were measured in patients with benign ovarian tumors, low malignant potential ovarian tumors (LMP), and ovarian carcinomas. Among 20 patients with pretreated recurrent ovarian carcinoma, 10 patients receiving treatment with paclitaxel (180 mg/m2) given once every 3 weeks (triweekly paclitaxel) and the other 10 patients receiving treatment with weekly paclitaxel (80 mg/m2) were randomly allocated. Sera from these patients were collected before treatment and 3 weeks after initiation of treatment to determine changes of VEGF and IL-8 levels. Although VEGF levels were highest in patients with ovarian carcinoma, there was no significant difference among benign, LMP, and carcinoma. Among patients with detectable levels of IL-8, ovarian carcinoma showed significantly higher IL-8 levels than benign tumors followed by LMP. VEGF levels in patients with treatment by triweekly paclitaxel did not show any significant change before and after treatment, while those in patients with treatment by weekly paclitaxel decreased significantly after treatment. Similarly, in patients with detectable IL-8 levels, weekly paclitaxel resulted in a significant decrease of IL-8 levels after treatment, while triweekly paclitaxel did not result in any significant change of IL-8 levels. The present study demonstrated that weekly but not triweekly paclitaxel had significant antiangiogenic effects.     

肺癌患者血浆中血管内皮生长因子与碱性纤维母细胞生长因子表达

目的　研究血管内皮生长因子 (VEGF)与碱性纤维母细胞生长因子 (bFGF)在肺癌患者血浆中表达水平。方法　采用定量免疫酶标 (ELISA)方法 ,检测 92例肺癌患者及肺部良性疾病血浆中VEGF与bFGF的含量。结果　 84例肺癌与 7例肺部良性疾病血浆中VEGF含量分别为 2 0 1.5± 183.0pg/ml,10 2 .5± 6 2 .5pg/ml,两者差异有显著性 (P <0 .0 5 ) ;其中 4 4例腺癌和 7例小细胞癌的VEGF含量分别为 2 0 2 .3± 177.0pg/ml、381.4± 314 .3pg/ml,与其肺部良性疾病比较 ,差异均有显著性 (分别为P <0 .0 5、P <0 .0 0 1)。在 5 6例肺癌与 4例肺部良性疾病血浆中bFGF含量分别为 4 5 .4± 2 3.9pg/ml,5 0 .4± 2 7.2pg/ml,两者差异无显著性。结论　在肺癌患者血浆中VEGF的含量明显高于肺部良性疾病的含量 ,其中腺癌和小细胞肺癌差异有显著性。而肺癌与肺部良性疾病无明显差异     

Vascular endothelial growth factor (VEGF) gene polymorphisms and gastric cancer risk in a Chinese Han population

The association between vascular endothelial growth factor (VEGF) gene polymorphisms and gastric cancer risk is still controversial and ambiguous. The objective of this study was to investigate the association between VEGF gene polymorphisms and gastric cancer risk in Chinese Han patients. We extracted the peripheral blood samples in 150 patients with gastric cancer and 150 controls. Polymerase chain reaction restriction fragment length polymorphism (PCR‐RFLP) analysis was performed to detect three VEGF gene polymorphisms (?634 G/C, +936 C/T, and +1612 G/A) in these patients. Patients with gastric cancer had a significantly higher frequency of 1612 AA genotype (OR = 6.26, 95% CI = 1.80, 21.85; P = 0.004) than controls. Patients with cardia gastric cancer had a significantly lower frequency of AA (OR = 0.11, 95% CI = 0.01, 0.89; P = 0.04) than those with noncardia gastric cancer. Patients with Lauren's diffuse‐type gastric cancer had a significantly higher frequency of AA (OR = 3.41, 95% CI = 1.22, 9.55; P = 0.02) than those with Lauren's intestinal‐type gastric cancer. The ?634 G/C and +936 C/T gene polymorphisms were not associated with a risk of GC and its progression. This study suggests that the VEGF +1612 G/A gene polymorphisms may be associated with gastric cancer in Chinese Han patients, and that difference in genotype distribution may be associated with the location and Lauren's classification of gastric cancer. Mol. Carcinog. © 2010 Wiley‐Liss, Inc.     

检测腹水中血管内皮生长因子对晚期卵巢癌维持治疗的临床意义

目的 评价检测腹水中血管内生长因子水平、腹腔灌注顺铂联合沙利度胺在晚期卵巢癌维持治疗中的临床意义。方法 回顾性分析不能耐受联合或强烈化疗、腹水检测血管内皮生长因子(VEGF)阳性的晚期卵巢癌患者69例的临床资料。腹腔灌注顺铂(DDP)联合沙利度胺(实验组)患者36例,单纯腹腔灌注顺铂患者(对照组)33例,具体方法如下:腹腔灌注顺铂40~60 mg/m²,1次/周,连续应用两次,4周为一周期,同时口服沙利度胺,治疗2个周期评价临床疗效、免疫功能及不良反应。结果 实验组有效率为72.2%,对照组有效率为46.9%,两组差异具有统计学意义。实验组、对照组治疗前与治疗2个周期后腹水VEGF水平相比,差异均具有统计学意义;实验组VEGF的下降幅度高于对照组VEGF的下降幅度。实验组、对照组治疗前与治疗2个周期后T淋巴细胞亚群百分率相比,差异均无统计学意义。实验组Ⅲ~Ⅳ级恶心呕吐发生率低于对照组,两组差异具有统计学意义;而实验组其它Ⅲ-Ⅳ级不良反应(如中性粒细胞减少、血红蛋白减少、疲倦)发生率与对照组相比,两组差异无统计学意义。结论 检测腹水中VEGF水平可提高恶性腹水的诊断率,腹腔灌注化疗药物联合沙利度胺治疗晚期卵巢癌恶性腹水有效率高,降低腹水中VEGF水平,提高生活质量,减轻不良反应,患者耐受性和依从性好。     

Functional significance of vascular endothelial growth factor receptors on gastrointestinal cancer cells

Vascular endothelial growth factor (VEGF) has been shown to be the major mediator of physiologic and pathologic angiogenesis. VEGF was initially thought to be an endothelial cell specific ligand, but recently, VEGF has been shown to mediate tumor cell function via activation of receptors on tumor cells themselves. Here, we review the expression patterns and binding profiles of the VEGF receptors and their ligands on gastrointestinal tumor cells. Furthermore, we describe the current knowledge in regards to the function of these receptors on tumor cells. Elucidating the function of VEGF receptors on tumor cells should help us to better understand the potential mechanisms of action of anti-VEGF therapies.     

Increased expression of vascular endothelial growth factor (VEGF) in bone marrow of patients with myeloproliferative disorders (MPD)

Angiogenesis is a multistep process of the development of capillaries from established blood vessels. Angiogenesis probably plays a significant role in the development and progression of hematopoietic malignancies. Higher microvascular density and increased serum levels of proangiogenic factors such as vascular endothelial growth factor (VEGF) or basic fibroblasts growth factor (bFGF) have been reported in acute and chronic leukemias, myeloproliferative and myelodysplastic disorders, multiple myeloma and lymphomas. The microvessel density of bone marrow stroma in myeloproliferative disorders is increased and VEGF is considered as the most potent endothelial cell activator. The purpose of this study was to examine the expression of VEGF in bone marrow of patients with MPD. 60 paraffinembedded bone marrow core biopsy specimens from newly diagnosed patients with MPD were evaluated. In addition 10 bone marrow core biopsy specimens from adult patients without evidence of malignancy were used as controls. Bone marrow sections were stained immunohistochemically for VEGF (PharMingen, USA). Obtained data show that MPD are associated with an increased expression of VEGF in the bone marrow. This observation support previous studies suggesting that angiogenesis may play a role in the pathophysiology of myeloproliferative disorders. Clinical significance of this phenomenon needs further investigation however thus provides rationale for use of angiogenesis inhibitors in MPD therapy.     

可溶性VEGF受体基因sflt-1与反义VEGF核苷酸对新生血管形成的影响

背景与目的:肿瘤组织中新生血管提供的大量营养物质和生长因子是肿瘤快速生长的关键,因此如何抑制肿瘤组织中新生血管的形成、促使肿瘤组织坏死也是肿瘤治疗中的一条值得探讨的途径。本文拟研究和观察可溶性血管内皮细胞生长因子(vascularendothelialgrowthfactor,VEGF)受体基因sflt-1与反义VEGF对新生血管形成的影响。方法:用Ad-反义VEGF感染肝癌细胞株MM45T.Li后,观察反义VEGF对MM45T.Li分泌VEGF的影响;将人工重组的3'ΔFlt-1蛋白(C末端缺失的Flt-1蛋白)加入条件培养液中,观察3'ΔFlt-1对VEGF刺激的脐静脉血管内皮细胞(humanumbilicalvascularendotheliumcell,HUVEC)增殖的影响;并将Ad-反义VEGF、Ad-sflt-1注射于鸡胚尿囊绒毛膜中,观察sflt-1、反义VEGF对鸡胚新生血管形成的影响。结果:反义VEGF重组腺病毒感染MM45T.Li细胞后,细胞培养上清中VEGF浓度仅为对照组中VEGF浓度的15%(P<0.01);在含有3'ΔFlt-1蛋白的调价培养液中,HUVEC的增殖明显减慢,在一定的范围内与剂量呈负相关;两者都能有效地抑制鸡胚新生血管的形成。结论:sflt-1与反义VEGF均能有效抑制新生血管的形成,两者联合能增强抑制效果,但其作用机制不同。     

VEGF directly suppresses activation of T cells from ovarian cancer patients and healthy individuals via VEGF receptor Type 2

The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis is well characterized; nevertheless, it is also a key element in promoting tumor evasion of the immune system by downregulating dendritic cell maturation and thus T cell activation. We sought to investigate the possible direct effect of VEGF on T cell activation and through which type of VEGF receptor (VEGFR) it exerts this effect. Circulating T cells from healthy donors and ovarian cancer patients were expanded in cultures with anti-CD3 and IL-2 with or without VEGF for 14 days, and the number of T cells was assessed. Cultured T cells were also tested for their cytotoxic activity in a standard 4-hr (51) Cr-release assay, and the expression of VEGFRs 1, 2 and 3 was assayed by flow cytometry, immunocytochemistry and Western blotting. To assess the ability of activated T cells to secrete VEGF, levels in culture supernatants were measured by enzyme linked immunosorbent assay. The addition of VEGF in cultures significantly reduced T cell proliferation in a dose-dependent manner. Protein expression studies demonstrated that CD3(+) T cells express VEGFR-2 on their surface upon activation. Experiments with anti-VEGFR-2 antibodies showed that the direct suppressive effect of VEGF on T cell proliferation is mediated by VEGFR-2. We also showed that VEGF significantly reduced the cytotoxic activity of T cells and that activated T cells secrete VEGF in the culture environment. Overall, our study shows that T cells secret VEGF and expresses VEGFR-2 upon activation. VEGF directly suppresses T cell activation via VEGF receptor type 2.     

血管内皮生长因子在子宫颈癌组织中的表达及意义

目的　探讨血管内皮生长因子 (VEGF ,VEGFmRNA)在子宫颈癌组织中的表达及意义。方法　采用免疫组织化学技术SP法及原位杂交方法检测 33例宫颈癌 ,其中鳞癌 2 0例 ,腺癌 13例及 10例正常宫颈组织中VEGF及VEGFmRNA的表达情况。结果　宫颈癌组织切片中VEGF及VEGFmRNA皆有活跃表达。正常宫颈组织中VEGFmRNA呈阴性表达 ,VEGF蛋白可见弱阳性表达 ,两组比较差异有显著性 (P <0 .0 5 ) ;宫颈癌组织切片中的VEGFmRNA的表达与宫颈癌病理类型比较差异有显著性 (P <0 .0 5 ) ;而与宫颈癌临床分期及病理分化程度比较差异无显著性 (P >0 .0 5 )。结论　VEGF及VEGFmRNA的阳性表达在子宫颈癌的发生 ,发展中可能有着重要的意义。VEGF的检测对判断宫颈癌的病理类型有一定的临床价值。     

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

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.