骨肉瘤与血管内皮生长因子、基质金属蛋白酶2、9表达的相关性研究

The expression of vascular endothelial growth factor,matrix metalloproteinases 2,9 in osteosarcoma

目的探讨骨肉瘤组织与血管内皮生长因子(VEGF)、基质金属蛋白酶(MMP)2、9表达的相关性及其对预后的影响,为骨肉瘤抗血管生成治疗的应用提供依据。方法采用免疫组织化学SP法对56例不同临床行为的骨肉瘤活检组织和8例转移灶组织进行VEGF、MMP-2、MMP-9表达的检测,并分析其与临床特点及预后的关系。结果经13～91个月随访,骨肉瘤患者3年无瘤生存率50.3%,5年无瘤生存率38.8%。MMP-2表达阳性率为53.6%,MMP-9表达阳性率为53.6%,VEGF高表达率为51.8%;MMP-2、MMP-9表达阳性和VEGF高表达与预后相关(P=0.0012、0.0049、0.0322)。MMP-2、MMP-9与VEGF的表达均有相关性(P=0.014、0.047)。COX比例风险模型分析影响骨肉瘤预后的因素有年龄(P=0.030)、MMP-2表达(P=0.024)和MMP-9表达(P=0.014),而性别、肿瘤大小、肿瘤亚型、手术方式和VEGF表达则与预后无关。骨肉瘤转移灶中MMP-2、MMP-9、VEGF表达阳性率较高,且同一病例原发灶与转移灶的表达有良好的一致性。结论骨肉瘤原发灶MMP-2、MMP-9表达提示肿瘤易于转移,患者预后差;骨肉瘤原发灶MMP-2、MMP-9表达与VEGF表达有相关性,提示前两者与VEGF在骨肉瘤转移过程的作用有关联;骨肉瘤转移灶MMP-2、MMP-9、VEGF表达阳性率较高。

Objective To investigate the expression of MMP-2, MMP-9 and VEGF in osteosarcoma and the correlation between VEGF and MMPs. Methods The expression of VEGF, MMP-2 and MMP-9 was detected by immunohistochemical method （S-P） in 56 patients of osteosarcoma including 8 with metastasis. The samples were collected from the primary osteosarcoma and the metastasis foci. Results The positive rates of MMP-2 and MMP-9 were 53.6% and 53.6%, respectively. And the high expression of VEGF was found in 51.8% of the cases. The clinical prognosis was associated with the positive expressions of MMP-2, MMP-9, and the high expression of VEGF by Log-Rank test. Moreover, the positive rates of MMP-2, MMP-9 and VEGF were higher in the metastasis foci than those in the primary tumors. In the same case, the expressions of MMP-2, MMP-9 and VEGF in the primary tumor were consistent with those in the metastasis foci, respectively. Kendall analysis indicated that the expressions of MMP-2 and MMP-9 were associated with the expression of VEGF in osteosarcoma. COX hazard regression analysis showed that： （1） sex, tumor size, tumor subtype, and the method of surgery were not related to prognosis; （2） the expression of MMP-2, MMP-9 in osteosarcoma and the age of patient were independently associated with poor prognosis and high rate of metastasis; （3） VEGF expression had no association with prognosis which was contradict with the result by Log-Rank test. Conclusion The high expressions of MMP-2 and MMP-9 in the primary osteosarcoma indicated high risk of metastasis and poor prognosis and the expressions of MMP-2 and MMP-9 were associated with that of VEGF expression.