HIF-1α、HPSE、VEGF共同促进视网膜母细胞瘤的恶性进程

HIF-1α, HPSE and VEGF promote malignant progression of retinoblastoma

目的探讨视网膜母细胞瘤（RB）中乙酰肝素酶（HPSE）、低氧诱导因子-1α（HIF-1α）的表达及其与血管内皮生长因子（VEGF）、微血管密度（MVD）的关系。方法应用免疫组织化学法检测34例RB石蜡标本及10例正常视网膜组织中HIF-1α、VEGF蛋白表达，用CD34抗体进行肿瘤血管内皮染色，计数肿瘤微血管密度（MVD）；应用RT—PCR检测18例RB组织中HPSEmRNA、HIF-1α mRNA、VEGFmRNA的表达，分析RB组织中HPSE、HIF-1α、VEGF表达情况及其与肿瘤微血管形成、临床及病理特征的关系。计量资料采用成组设计定量资料t检验、方差分析和q检验；计数资料采用X^2检验、Fisher检验及秩和检验；相关性采用Spearman等级相关分析及kappa检验。结果34例RB石蜡标本中HIF—1α、VEGF阳性表达率为58．8％、64．7％，明显高于正常对照组（X^2=10．784，P〈0．05；X^2=9．269，P〈0．05）。18例RB中HPSE、HIF-1α、VEGFmRNA阳性率为55．6％、44．4％、72．2％，与正常组比较有统计学意义（X^2=8．642，P〈0．05；X^2=6．222，P〈0．05；X^2=9．956，P〈0．05）。HIF-1α、VEGF与MVD的表达呈正相关（r=0．664，P〈0．05；r=0．590，P〈0．05）；RB中HIF-1α mRNA、HPSEmRNA表达与VEGFmRNA表达呈相关性（Z=2．350，P=0．009；Z=2．940，P=0．002）。结论HIF-1α、HPSE可共同作用于VEGF这种促血管生成重要因子，在肿瘤血管形成中起一定作用。

Objective To investigate the expression of heparanase （HPSE）, hypoxia-inducible factor （HIF-1α） and their correlation with expression of vascular endothelial growth factor （VEGF） and microvessel density （MVD） in retinoblastoma. Methods HIF-1α and VEGF were detected by SP immunohistochemical method in 34 cases of retinoblastoma and 10 cases of normal retina tissues. MVD was measured by anti-CD34. Eighteen samples of retinoblastoma tissues and ten samples of normal retina were examined for HPSE mRNA, HIF-1α mRNA, VEGF mRNA expression by RT-PCR. The correlation between HPSE, HIF-1α and VEGF expression, MVD and clinical and pathological characters were analyzed. The statistical methods are the measurement data using grouped quantitative data t test, variance analysis and q test; enumeration data compared with X^2 test, Fisher test and rank sum test; correlation analysis using Spearman rank correlation analysis and the kappa test. Results The positive expression rates of HIF-1α and VEGF were 58. 8%, 64. 7% higher in retinoblastoma than in normal retina＇s （X^2 = 10. 784,P 〈0.05; X^2 = 9. 269,P 〈 0. 05 ）. Positive expression of HPSE, HIF-1α, VEGF mRNA were found in 55.6% ,44. 4% 72. 2%. The expression of HIF-1α and VEGF in retinoblastoma were correlated with MVD（r = 0. 664, P 〈 0. 05 ;r = 0. 590, P 〈 0. 05 ）. VEGF was correlated with HPSE and HIF-1α （ Z = 2. 350, P = 0. 009 ; Z = 2. 940, P = 0. 002）. Conclusions HPSE and HIF-1α can influence the expression of VEGF, an important angiogenesis factor. HPSE, HIF-1α and VEGF play a role in tumor angiogenesis and promote malignant progress of retinoblastoma.