脉络膜黑色素瘤血管生成因素与其预后指标关系探讨

Correlation of tumor angiogenesis with clinicopathologic prognostic parameters in choroidal melanoma

目的 探讨血管内皮生长因子 (vascularendothelialgrowthfactor,VEGF)mRNA及VEGF在脉络膜黑色素瘤中的表达 ,分析血管生成因素与脉络膜黑色素瘤临床及组织病理学预后指标间的关系。方法 应用免疫组织化学和原位分子杂交技术 ,检测 6 5例脉络膜黑色素瘤患者瘤组织中VEGFmRNA、VEGF的表达 ;应用第Ⅷ因子相关抗原 (factorⅧ relatedantigen ,FⅧ RAg)抗体标记瘤体血管内皮细胞 ,计数微血管密度 (microvesseldensity ,MVD)。结果 VEGFmRNA与VEGF表达阳性率分别为 86 %和 85 % ;VEGF表达阳性的肿瘤MVD值明显高于阴性者 (单因素方差分析 ,P =0 0 0 0 ) ;不同体积的肿瘤表达VEGF阳性率的差异有显著意义 (P =0 0 2 5 ) ;是否伴有巩膜导管受侵的肿瘤表达VEGF阳性率的差异也有显著意义 (P =0 0 34) ;而不同最大基底直径 (largesthumordiameter,LTD)、不同细胞类型、不同位置的肿瘤表达VEGF阳性率的差异均无显著意义 ;不同LTD、不同体积、不同细胞类型、是否侵犯巩膜导管其肿瘤的MVD值的差异有显著意义 (t检验 ,P值分别为 0 0 12、0 0 0 8、0 0 0 1和0 0 0 0 ) ,与不同患者年龄和不同位置其肿瘤的MVD值的差异无显著意义。结论 脉络膜黑色素瘤血管生成因素与其临床及组织病理学预后指标有密切关系 。

ObjectiveTumor angiogenesis is an essential step for tumor growth, progression and metastasis. Vascular endothelial growth factor (VEGF) is a mitogen specific for vascular endothelial cells, and plays a key role in tumor angiogenesis. The purpose of the present study was to investigate the expression of VEGF mRNA and VEGF protein in choroidal melanoma and to correlate these factors and the microvessel density (MVD) with the clinicopathologic prognostic features.MethodsIn a total of 65 cases of choroidal melanoma from the Pathology Laboratory of Tongren Hospital, the expression of VEGF mRNA was assessed by in situ hybridization (ISH); the expression of VEGF protein and factor Ⅷ-related antigen (FⅧ-RAg) was assessed using immunohistochemical methods. MVD was evaluated by immunohistochemical staining of FⅧ-RAg for vascular endothelial cells. ResultsVEGF mRNA expression was present in 56/65 cases (86%), while VEGF immunoreactivity was present in 55/65 cases (85%). Positive expression of VEGF and VEGF mRNA was correlated with the tumor size (P=0.025) and local invasion of tumor to scleral emissaria (P=0.034), but it′s relation to the histologic type, the tumor location and the largest tumor diameter (LTD) was not statistically significant. MVD was significantly higher in the VEGF-positive melanoma than in the VEGF-negative melanoma (one way analysis of variance, P=0.000). There was no significant correlation between MVD and tumor location, as well as the tumor height and the patient′s age; however, significant correlation was found between MVD and LTD, as well as with the tumor size, cell type and the invasion of tumor to the scleral emissaria (t test, P=0.012, 0.008, 0.001 and 0.000, respectively). ConclusionsMost choroidal melanomas express VEGF mRNA and VEGF protein, and this expression is correlated with MVD. This suggests that angiogenesis is significantly correlated with clinicopathologic prognostic factors of choroidal melanoma, such as LTD, tumor size,cell type and tumor invasion. MVD and the expression of VEGF may be useful prognostic indicators for the biological behavior and the outcome of choroidal melanoma.