星形细胞肿瘤微血管参数与VEGF阳性单位的关系及CD34～+细胞三维分布
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摘要
星形细胞肿瘤是人脑最常见的肿瘤之一,以其生长部位特殊性和生长具有侵袭性对人体构成极大的危害。而具有丰富血管是恶性星形细胞肿瘤生长演进过程中的一个特征,主要是在血管内皮生长因子(vascular endothelial growth factor,VEGF)与VEGF受体的结合后促血管内皮细胞增殖分化、血管成型而成。组织芯片(tissue chips),或称组织微阵列(tissue microarray),以其高通量的特性使得科研人员能同时对大量标本的基因、基因转录及蛋白表达水平进行研究并能进行很好的质控,从而提高研究结果的可靠性。因此,利用免疫组织化学双染技术在组织芯片上定量分析微血管构筑参数以及VEGF表达情况,能对胶质瘤的诊断、疗效评估等提供客观的依据。
肿瘤微血管新生化在肿瘤组织中是一个渐进的过程,即在肿瘤的不同部位,微血管处于一种发生、成熟、退化的渐进过程。利用组织连续切片对不同阶段的微血管中内皮细胞在肿瘤组织中的分布情况进行三维重建,能从空间构型上显示组织中微血管内皮细胞,在深入探讨细胞因子与血管生成的发生、发展、转归以及临床预后、疗效评估等各方面中有着重要的意义。
本研究以不同级别和不同微血管形态的星形细胞肿瘤组织为材料构建组织芯片,在其基础上应用免疫双标技术和图像分析方法对微血管数目、微血管平均周长和VEGF阳性单位(positive unit,PU)值进行定量分析,且应用三维重建技术对总厚度为210μm的连续切片肿瘤组织中CD34阳性细胞的空间分布进行重建。主要结果和结论如下:
一、构建出含不同分化程度人脑星形细胞肿瘤不同微血管形态的168点组织芯片,并通过其对组织中微血管构筑参数和VEGF表达进行定量分析
以80例(弥漫型星形细胞瘤31例,间变型星形细胞瘤32例,胶质母细胞瘤17例)人脑星形细胞肿瘤按不同微血管形态构建出组织芯片,共168点,其中微血管形态包括薄壁血管104点、厚壁血管40点、肾小球样血管11点、血管心假菊形团样结构血管5点。所制芯片点阵排列为薄壁血管WHOⅡ级43点、WHOⅢ级38点、WHOⅣ
Astrocytomas are the most common brain tumors, which are characterized by invasive growth and active angiogenesis. Antiangiogenesis, a new strategy for treatment of astrocytomas depend on better understanding of angiogenesis. It is known that angiogenesis results from an imbalance of proangiogenic and antiangiogenic factors. One of the most important regulatory factors is vascular endothelial growth factor (VEGF), which can induce the migration, proliferation and differentiation of endothelial cells or their progenitors. Most of the results of relationship between expression of VEGF and grades of astrocytomas were from qualitative or semiquantitative analysis, therefore, further quantitative studies are needed.
We defined the concept of tumor microvascular architecture phenotype heterogeneity (T-MAPH) as heterogeneities of the density, morphology, structure and the three-dimensional distribution of newly formed vessels in a tumor and between tumors. The pattern of T-MAPH may represent the invasiveness of the tumor therefore predict the outcome of therapy. The 3D distribution of CD34 positive cells is a basis of the understanding for T-MAPH.
In the present study, we constructed the tissue microarray, or tissue chip, containing different grades of human astrocytomas with different architecture features of microvessels for the usage of quantitative analysis of microvessel parameters and the expression of VEGF. The main results and conclusions are as follows:
1. A tissue microarray composed of 168 points was constructed with human astrocytoma tissues. The microarray includes different grades of astrocytoma with different microvessel types, such as sinusoid, thick-wall and glomeruliod microvessels, etc.
肿瘤微血管新生化在肿瘤组织中是一个渐进的过程,即在肿瘤的不同部位,微血管处于一种发生、成熟、退化的渐进过程。利用组织连续切片对不同阶段的微血管中内皮细胞在肿瘤组织中的分布情况进行三维重建,能从空间构型上显示组织中微血管内皮细胞,在深入探讨细胞因子与血管生成的发生、发展、转归以及临床预后、疗效评估等各方面中有着重要的意义。
本研究以不同级别和不同微血管形态的星形细胞肿瘤组织为材料构建组织芯片,在其基础上应用免疫双标技术和图像分析方法对微血管数目、微血管平均周长和VEGF阳性单位(positive unit,PU)值进行定量分析,且应用三维重建技术对总厚度为210μm的连续切片肿瘤组织中CD34阳性细胞的空间分布进行重建。主要结果和结论如下:
一、构建出含不同分化程度人脑星形细胞肿瘤不同微血管形态的168点组织芯片,并通过其对组织中微血管构筑参数和VEGF表达进行定量分析
以80例(弥漫型星形细胞瘤31例,间变型星形细胞瘤32例,胶质母细胞瘤17例)人脑星形细胞肿瘤按不同微血管形态构建出组织芯片,共168点,其中微血管形态包括薄壁血管104点、厚壁血管40点、肾小球样血管11点、血管心假菊形团样结构血管5点。所制芯片点阵排列为薄壁血管WHOⅡ级43点、WHOⅢ级38点、WHOⅣ
Astrocytomas are the most common brain tumors, which are characterized by invasive growth and active angiogenesis. Antiangiogenesis, a new strategy for treatment of astrocytomas depend on better understanding of angiogenesis. It is known that angiogenesis results from an imbalance of proangiogenic and antiangiogenic factors. One of the most important regulatory factors is vascular endothelial growth factor (VEGF), which can induce the migration, proliferation and differentiation of endothelial cells or their progenitors. Most of the results of relationship between expression of VEGF and grades of astrocytomas were from qualitative or semiquantitative analysis, therefore, further quantitative studies are needed.
We defined the concept of tumor microvascular architecture phenotype heterogeneity (T-MAPH) as heterogeneities of the density, morphology, structure and the three-dimensional distribution of newly formed vessels in a tumor and between tumors. The pattern of T-MAPH may represent the invasiveness of the tumor therefore predict the outcome of therapy. The 3D distribution of CD34 positive cells is a basis of the understanding for T-MAPH.
In the present study, we constructed the tissue microarray, or tissue chip, containing different grades of human astrocytomas with different architecture features of microvessels for the usage of quantitative analysis of microvessel parameters and the expression of VEGF. The main results and conclusions are as follows:
1. A tissue microarray composed of 168 points was constructed with human astrocytoma tissues. The microarray includes different grades of astrocytoma with different microvessel types, such as sinusoid, thick-wall and glomeruliod microvessels, etc.
引文
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