血管内皮生长因子对骨肉瘤的血管生成及转移预后的影响

Effects of VEGF Expression on Angiogenesis,Tumor Growth and Metastasis in Osteosarcoma

目的 :研究血管内皮生长因子 (VEGF)对骨肉瘤血管生成、生长、转移及预后的影响。方法 :对 69例骨肉瘤患者的临床病理资料进行回顾性研究 ,应用CD3 4、VEGF单克隆抗体对其组织切片分别进行免疫组化染色 ,应用地高辛标记的VEGF探针对 2 7例原发性骨肉瘤进行原位杂交染色。分析研究了VEGF表达与CD3 4染色阳性的血管密度的关系 ,所有上述临床病理资料及染色结果与患者预后情况进行统计学分析。结果 :在 3 9例 (5 6.5 % )VEGF表达阳性的标本中 ,CD3 4染色阳性的肿瘤微血管密度 (MVD)明显较 3 0例VEGF表达阴性的血管密度高 (P <0 .0 5 )。多元回归分析显示 ,血管密度 (MVD)增高及VEGF表达阳性与骨肉瘤患者的远隔转移发生、不良预后密切相关 (P <0 .0 5 )。临床病理资料中 ,外科手术边界微小病灶阳性情况、Enneking外科分期、肿瘤大小和患者年龄与患者预后相关 (P <0 .0 5 )。患者性别、手术方法分类以及病理亚型与预后无相关性。结论 :VEGF在骨肉瘤的血管生成和转移中起到重要作用 ,VEGF是骨肉瘤血管生成的决定性刺激因子 ,骨肉瘤微血管密度 (MVD)和骨肉瘤组织中VEGF表达情况是骨肉瘤患者的独立性预后因素。

Objective:To investigate the role of vascular endothelial growth factor(VEGF)on angiogenesis,tumor growth and metastasis in osteosarcoma,and its clinical significance.Methods:Sixty-nine specimens of primary osteosarcomas were studied with immunohistochemistry and in situ hybridization techniques.The correlation between the expression of VEGF and the density of CD34-positive microvessels,the prognostic significance of VEGF expression,microvessel density(MVD)and clinicopathological variables were evaluated.Results:VEGF staining was positive in 39 tumors(56.5%)in which the CD34-positive microvessels was significantly higher than that in VEGF-negative 30 tumors ( P <0.05),and multivariate analysis indicated that microvessel density(MVD)and VEGF expression were closely correlated with patients' poor prognosis as well as metastasis.In terms of clinicopathological variables,the microscopic surgical margin appearance,Enneking stage,tumor size and patient's age were correlated with the patient's prognosis( P <0.05),particularly,the microscopic surgical margin appearance had more prognostic significance especially in predicting metastasis and local relapse.There was no correlation between patient's prognosis and patient's gender,surgical definition and histologic type.Conclusions:VEGF is a critical angiogenic stimuli which stimulates angiogenesis,tumor growth and metastasis in osteosarcoma,the microvessel density(MVD)and VEGF expression can function as two independent prognostic variables in osteosarcoma.