Tirakotai Wuttipong, Fremann Sandra, Soerensen Niels, Roggendorf Wolfgang, Siegel Adrian M, Mennel Hans Dieter, Zhu Yuan, Bertalanffy Helmut, Sure Ulrich
Department of Neurosurgery, Philipps University, Baldingerstrasse, 35033, Marburg, Germany.
Childs Nerv Syst. 2006 Jul;22(7):685-91. doi: 10.1007/s00381-006-0044-4. Epub 2006 Feb 18.
According to the hypothesis that paediatric cerebral cavernomas may have different biological activity compared to adult cavernomas, immunohistochemical analysis was used to elucidate the biological nature of paediatric cavernomas.
We examined the histological features and the proliferative and angiogenic capacity of the tissue specimens acquired from 28 paediatric patients. Normal paediatric brain tissues obtained from paediatric autopsy cases were used as a control group. The proliferative activity of the endothelium and the neoangiogenetic capacity were investigated by immunohistochemistry for proliferating cell nuclear antigen (PCNA), Ki-67 epitope (MIB-1), Flk-1 receptor, vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1 alpha, and endoglin antibody, respectively. Afterwards, the results of the paediatric lesions were analysed and compared with the correspondent values of previously reported immunohistochemical analysis in adult cavernomas.
Positive immunostaining of VEGF was detected significantly less in paediatric cavernomas compared to adult cases (p<0.05). In contrast, endoglin, a protein that is upregulated during an increased vascular shear stress, was expressed more often in paediatric cavernomas (p<0.05). Neither the expression of the PCNA nor the expression of the HIF-1alpha was found significantly different between paediatric and adult cavernomas. However, the positive immunoreaction for MIB-1 occurred more often in the paediatric cases (p<0.05).
The immunohistochemical study indicates that paediatric cavernomas are dynamic lesions. The VEGF/Flk-1 associated neoangiogenesis may play a minor role for the biology of paediatric cavernomas, while endoglin seems to act more prominently than previously thought, particularly for the biology of paediatric cavernomas.
基于小儿脑海绵状血管瘤可能与成人海绵状血管瘤具有不同生物学活性这一假设，采用免疫组化分析来阐明小儿海绵状血管瘤的生物学特性。
我们检查了从28例小儿患者获取的组织标本的组织学特征、增殖能力和血管生成能力。取自小儿尸检病例的正常小儿脑组织用作对照组。分别通过免疫组化检测增殖细胞核抗原（PCNA）、Ki-67抗原决定簇（MIB-1）、Flk-1受体、血管内皮生长因子（VEGF）、缺氧诱导因子（HIF）-1α和内皮糖蛋白抗体，来研究内皮细胞的增殖活性和新生血管生成能力。之后，分析小儿病变的结果，并与先前报道的成人海绵状血管瘤免疫组化分析的相应值进行比较。
与成人病例相比，小儿海绵状血管瘤中VEGF的阳性免疫染色显著较少（p<0.05）。相反，内皮糖蛋白是一种在血管剪切应力增加时上调的蛋白质，在小儿海绵状血管瘤中更常表达（p<0.05）。未发现小儿和成人海绵状血管瘤之间PCNA的表达或HIF-1α的表达有显著差异。然而，小儿病例中MIB-1的阳性免疫反应更常见（p<0.05）。
免疫组化研究表明小儿海绵状血管瘤是动态病变。VEGF/Flk-1相关的新生血管生成可能在小儿海绵状血管瘤的生物学过程中起次要作用，而内皮糖蛋白的作用似乎比先前认为的更为突出，特别是在小儿海绵状血管瘤的生物学过程中。
