[HIF-1alpha, HPSE and VEGF promote malignant progression of retinoblastoma].
OBJECTIVE
To investigate the expression of heparanase (HPSE), hypoxia-inducible factor (HIF-1alpha) and their correlation with expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in retinoblastoma.


METHODS
HIF-1alpha 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-1alpha mRNA, VEGF mRNA expression by RT-PCR. The correlation between HPSE, HIF-1alpha 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 chi(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-1alpha and VEGF were 58.8%, 64.7% higher in retinoblastoma than in normal retina's (chi(2) = 10.784, P < 0.05; chi(2) = 9.269, P < 0.05). Positive expression of HPSE, HIF-1alpha, VEGF mRNA were found in 55.6%, 44.4%, 72.2%. The expression of HIF-lalpha 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-1alpha (Z = 2.350, P = 0.009; Z = 2.940, P = 0.002).


CONCLUSIONS
HPSE and HIF-1alpha can influence the expression of VEGF, an important angiogenesis factor. HPSE, HIF-1alpha and VEGF play a role in tumor angiogenesis and promote malignant progress of retinoblastoma.
Wang
Xiao-lei
XL
Department of Ophthalmology, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266021, China. xiaoshitou9966@yahoo.com.cn
Niu
Ying-jun
YJ
Ma
Jian-min
JM
D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D019572:Retinal Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D012175:Retinoblastoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D000099175:Heparanase
D005966:Glucuronidase; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D000099175:Heparanase; C497442:HIF1A protein, human; C467484:VEGFA protein, human