Correlation Of Tumor Angiogenesis With Clinicopathologic Prognostic Parameters In Retinoblastoma

Objective: Angiogenesis is essential for tumor growth, progression andmetastasis and depends on the production of angiogenic factors by tumor cells. Vascular endothelial growth factor (VEGF) is a mitogen specific for vascular endothelial cells, and play a critical role in tumor angiogenesis. The purpose of present study is to evaluate the expression of VEGF protein in retinoblastoma (RB), which is the commonest intraocular tumor in young children and has a clear tendency for metastatic spread to the skull, and to find the correlation of VEGF and the microvessel density(MVD) with the clinicopathologic prognostic features of this disease. Methods: Thirty-two patients with retinoblastoma were followed-up for at least 5 years. The paraffin sections of those patients with anti-CD34-McAb and anti-VEGF-McAb were immunohistochemically stained respectively, MVD was determined by counting tumor vessels in a masked fashion from areas of highest vessel density after immunostaining for CD34 epftope, and the average optical density (OD) of VEGF-positive cell were measured with the pathological image analysis system. The association between MVD and OD with tumor size, cell type, clinical stage, optic nerve infiltration, choroid invasion was assessed. Kaplan-Meier and log-rank test were performed. The data of our research subsequently were analyzed with the statistic software detaitedly. Resvfts: Expression of VEGF was present in 27/32 cases (84.4%) and significantly associated with the tumor diameter, optic nerve invasion, choroids infiltration, metastasis and patients survival(P =0.003, 0.046, 0.044, 0.003, 0.002). Its relationship to cell type, radiotherapy and relapse were not statistically significant. There was no correlation in MVD with cell type; howerve significant correlation was found between MVD and tumor size, as well as optic nerve infiltration, choroids invasion, metastasis, relapse,radiotherapy and survival (P =0.000, 0.000, 0.001, 0.027,0.003,0.003,0.000). The univariaie statistical analysts of the log-rank test showed that MVD, VEGF, optic nerve infiltration, choroids invasion, tumor size were statistically significant variables for the survival of the patients with RB(p=0.0129,0.0361, 0.001, 0.0243, 0.0168). The stepwise linear regression equation showed that the MVD value correlated positively to the OD value(P=0.013). Conelusion Most retinoblastomas express VEGF protein, and this expression is correlated with MVD. Both the expression of VEGF and the MVD are significantly correlated with clinicopathotogic factors of RB , and have statistically significant correlation to the survival of patients with RB. Along with other accepted prognostic information, MVD and the expression of VEGF could be prognostic indicators for the biological behavior and the outcome of retinoblastoma. We conclude that microvessel density and VEGF are useful prognostic factors for the survival of patients with retinoblastoma and help identify the high-risk patients for whom adjuvant therapy should be considered.