Kaya M, Wada T, Akatsuka T, Kawaguchi S, Nagoya S, Shindoh M, Higashino F, Mezawa F, Okada F, Ishii S
Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Hokkaido, Japan.
Clin Cancer Res. 2000 Feb;6(2):572-7.
To investigate the clinical significance of vascular endothelial growth factor (VEGF) in osteosarcoma, we immunohistochemically stained biopsy specimens of 27 primary osteosarcomas using an antibody against VEGF and evaluated the correlation between the expression of VEGF and local density of CD34-positive microvessels, clinicopathological variables, and survival of patients. VEGF staining was positive in 17 tumors (63.0%) in which the density of CD34-positive microvessels was significantly higher than that in VEGF-negative 10 tumors (P < 0.05). In terms of clinicopathological variables, there was no correlation between the expression of VEGF and histological subtype, stage, or response to neoadjuvant chemotherapy, or, strikingly, to the development of pulmonary metastasis (89% of VEGF-positive tumors versus 10% of VEGF-negative tumors; P < 0.0003). Moreover, patients with a VEGF-positive tumor were poorer in both disease-free survival (P < 0.001) and overall survival (P < 0.03) compared to those with a VEGF-negative tumor. These findings strongly suggest that VEGF expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis in patients who underwent aggressive therapy and also provide the basis for a therapeutic strategy targeting angiogeneic property of osteosarcoma.
为了研究血管内皮生长因子（VEGF）在骨肉瘤中的临床意义，我们使用抗VEGF抗体对27例原发性骨肉瘤的活检标本进行免疫组织化学染色，并评估VEGF表达与CD34阳性微血管局部密度、临床病理变量以及患者生存率之间的相关性。17例肿瘤（63.0%）VEGF染色呈阳性，其中CD34阳性微血管密度显著高于10例VEGF阴性肿瘤（P<0.05）。在临床病理变量方面，VEGF表达与组织学亚型、分期、对新辅助化疗的反应，或者显著地，与肺转移的发生之间均无相关性（VEGF阳性肿瘤为89%，VEGF阴性肿瘤为10%；P<0.0003）。此外，与VEGF阴性肿瘤患者相比，VEGF阳性肿瘤患者的无病生存期（P<0.001）和总生存期（P<0.03）均较差。这些发现强烈表明，未经治疗的骨肉瘤中VEGF表达可预测接受积极治疗患者的肺转移和不良预后，也为针对骨肉瘤血管生成特性的治疗策略提供了依据。
