Department of Pediatrics, Beatrix Children's Hospital, Pediatric Oncology Division, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Neuropathol Appl Neurobiol. 2010 Dec;36(7):636-47. doi: 10.1111/j.1365-2990.2010.01113.x.
Pilocytic astrocytomas are the most frequent brain tumours in children. Because of their high vascularity, this study aimed to obtain insights into potential angiogenic related therapeutic targets in these tumours by characterization of the vasculature and the angiogenic profile. In this study 59 paediatric pilocytic astrocytomas were compared with 62 adult glioblastomas, as a prototype of tumour angiogenesis.
Microvessel density, vessel maturity in terms of basement membrane and pericyte coverage, and turnover of both endothelial and tumour cells, and vascular endothelial growth factor (VEGF) expression were evaluated in tumour tissue, immunohistochemically stained with, respectively, CD34, collagen IV, smooth muscle actin, Ki67/CD34, caspase-3/CD34 and VEGF(-A-D). As an indicator for vessel stability the angiopoietin (ANGPT)-1/ANGPT-2 balance was calculated using Real Time RT-PCR.
Pilocytic astrocytoma and glioblastoma showed similar fractions of vessels covered with basement membrane and pericytes. Overlapping ANGPT-1/ANGPT-2 balance and VEGF-A expression were found. Pilocytic astrocytoma had fewer but wider vessels compared with glioblastoma. Turnover of endothelial and tumour cells were relatively lower in pilocytic astrocytoma. Within pilocytic astrocytoma, higher ANGPT-1/ANGPT-2 balance was correlated with fewer apoptotic endothelial cells. Lower numbers of vessels were correlated with higher VEGF-A expression.
Despite the fact that pilocytic astrocytoma showed a different vessel architecture compared with glioblastoma, a critical overlap in vessel immaturity/instability and the angiogenic profile was seen between both tumours. These findings suggest encouraging possibilities for targeting angiogenesis (for instance with anti-VEGF) as a therapeutic strategy in pilocytic astrocytoma.
毛细胞星形细胞瘤是儿童中最常见的脑肿瘤。由于其高度血管化，本研究旨在通过对血管和血管生成特征的描述，了解这些肿瘤中潜在的血管生成相关治疗靶点。本研究比较了 59 例儿童毛细胞星形细胞瘤和 62 例成人胶质母细胞瘤，后者是肿瘤血管生成的典型代表。
应用免疫组化方法，分别用 CD34、胶原 IV、平滑肌肌动蛋白、Ki67/CD34、caspase-3/CD34 和血管内皮生长因子（VEGF）（-A-D）对肿瘤组织中微血管密度、基底膜和周细胞覆盖的血管成熟度以及内皮细胞和肿瘤细胞的更新进行评估。采用实时 RT-PCR 计算血管生成素（ANGPT）-1/ANGPT-2 平衡作为血管稳定性的指标。
毛细胞星形细胞瘤和胶质母细胞瘤的基底膜和周细胞覆盖的血管比例相似。发现重叠的 ANGPT-1/ANGPT-2 平衡和 VEGF-A 表达。与胶质母细胞瘤相比，毛细胞星形细胞瘤的血管数量较少，但更宽。内皮细胞和肿瘤细胞的更新率在毛细胞星形细胞瘤中相对较低。在毛细胞星形细胞瘤中，较高的 ANGPT-1/ANGPT-2 平衡与较少的凋亡内皮细胞相关。较少的血管数量与较高的 VEGF-A 表达相关。
尽管毛细胞星形细胞瘤与胶质母细胞瘤相比具有不同的血管结构，但两种肿瘤的血管不成熟/不稳定和血管生成特征存在显著重叠。这些发现表明，针对血管生成（例如抗 VEGF）作为治疗策略在毛细胞星形细胞瘤中具有令人鼓舞的可能性。
