Heterogeneous tumor vasculature in retinoblastoma -: Implications for vessel targeting therapy
Heterogeneous tumor vasculature in retinoblastoma -: Implications for vessel targeting therapy
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DOI：
10.1097/iae.0b013e318150d6f0
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发表时间：
2008-03-01
影响因子：
3.3
通讯作者：
Murray, Timothy G.
中科院分区：
文献类型：
--
作者：
Jockovich, Maria-Elena;Pina, Yolanda;Murray, Timothy G.
目的：探讨视网膜母细胞瘤肿瘤标本的肿瘤大小与血管成熟度的关系，探讨这些因素对血管靶向治疗的影响。肿瘤大小作为肿瘤的最大横截面积，在病理评估中测量。免疫组织化学方法检测血管密度和异质性。用单叶班德拉凝集素对内皮细胞进行染色，检测总微血管密度；用内皮细胞标记物endoglin(CD105)检测新的血管形成。血管基底膜用IV型胶原抗体检测。结果：肿瘤负荷与摘除时的年龄显著相关(P=0.008)。所有视网膜母细胞瘤肿瘤样本都含有高度的血管异质性，包括未成熟的新生血管和周细胞定位的成熟血管。IV型胶原与眼球摘除时的年龄有显著相关性(P=0.045)。结论：本研究为更好地了解视网膜母细胞瘤的肿瘤和血管发育提供了一个框架。这项研究的结果为这些肿瘤中年龄和肿瘤负担之间的关系提供了洞察力。了解在这些肿瘤中检测到的异质性程度将有助于为患有这种疾病和其他具有病理性新生血管的疾病的儿童选择新的血管靶向策略。
Purpose: The aim of this study is to correlate tumor size of retinoblastoma tumor samples with blood vessel maturation to assess how these factors may affect vessel targeting therapy.Methods: Analysis was performed on retinoblastoma tumor specimens (n = 5) enucleated as primary treatment from May 2005 to February 2006. Tumor size was measured as the largest cross sectional area of the tumor, measured during pathologic assessment. Vessel density and heterogeneity was measured by immunohistochemical analysis. Total microvessel density was detected by staining endothelial cells using a lectin from Bandeira simplicifolia; novel vasculature was detected with the endothelial cell marker endoglin (CD1 05). Blood vessel basement membrane was detected with an antibody against type IV collagen. Vessel maturation was assessed by pericyte recruitment, detected with a smooth muscle actin (alpha-sma).Results: A statistically significant correlation was detected between tumor burden and age at enucleation (P = 0.008). All retinoblastoma tumor samples harbored a high degree of blood vessel heterogeneity containing both immature neovessels as well as pericyte-committed mature vasculature. There was a statistically significant correlation between type IV collagen and age at enucleation (P = 0.045).Conclusions: This study provides a framework for a better understanding of tumor and vessel development in retinoblastoma. Results of this study provide insight into the relationship between age and tumor burden in these tumors. Knowledge of the degree of heterogeneity detected in these tumors will aid in the selection of novel blood vessel targeting strategies for children with this disease and other diseases with pathologic neovascularization.