骨肉瘤中HIF-1α、VEGF、p53表达与血管生成和预后的关系

Expression of hypoxia-inducible factor 1α, VEGF and p53 and their association with angiogenesis and prognosis in osteosarcoma

目的 检测缺氧诱导因子 1α(HIF 1α)及VEGF、p5 3、CD34在骨肉瘤的表达 ,探讨其与缺氧情况下骨肉瘤血管生成和预后的关系。方法 采用免疫组织化学S P法检测 4 6例有完整随访资料的骨肉瘤病例中HIF 1α、VEGF、p5 3、CD34的表达。用Spearman分析各指标间的相关性 ,并结合临床资料进行生存曲线分析。结果 4 6例骨肉瘤标本中有 14例 (30 4 % )表达HIF 1α ;HIF 1α表达组VEGF、p5 3表达强度及术后转移率均高于HIF 1α不表达组 ;HIF 1α表达组患者术后 1年生存率及总生存率均显著低于HIF 1α不表达组。HIF 1α表达与VEGF、p5 3表达之间存在显著相关性 ;HIF 1α表达与微血管密度(MVD)之间无相关性。结论骨肉瘤组织中存在HIF 1α的过表达 ,HIF 1部分地参与了骨肉瘤的演进 ,HIF 1通过调节VEGF的表达在骨肉瘤血管生成中发挥着重要作用 ;HIF 1和p5 3缺失或突变可能协同参与了缺氧对骨肉瘤肿瘤细胞的调节 ,HIF 1α表达与骨肉瘤的不良预后密切相关 。

Purpose To detect the expression of hypoxia-inducible factor 1α (HIF-1α) and VEGF, p53 and CD34 in osteosarcoma and to investigate their association with angiogenesis and prognosis of osteosarcoma under hypoxia.. Methods Immunohistochemical staining (S-P method) was used to detect HIF-α and VEGF, p53 and CD34 expression in 46 cases of osteosarcoma which had complete follow-up data. Spearman coeffcient of correlation was used to test correlation between HIF-1α and VEGF, p53, MVD. Follow-up data were collected to perform survival curve analysis. Results Expression of HIF-1α was observed in 14(30.4%)cases. Patients with expression of HIF-1α had a higher VEGF and p53 expression and metastasis rate since surgery compared with those with no expression. Patients with expression of HIF-1α had a significantly shorter one-year survival and overall survival rate since surgery compared with those with no expression. HIF-1α expression was found significant association with VEGF and p53 expression, but no correlation with MVD. Conclusion There is HIF-1α overexpression in osteosarcoma. HIF-1 is involved in the progression of osteosarcoma partly. HIF-1 play a very important role in angiogenesis of osteosarcoma through regulating the expression of VEGF. HIF-1 cooperates with p53 deletion or mutation taking part in the regulation of osteosarcoma tumor cells under hypoxia probably. There is an intimate correlation between the expression of HIF-1α in osteosarcoma and its unfavorable prognosis. HIF-1α expression is an useful parameter to evaluate prognosis of osteosarcoma.