Differentiation between high- and low-grade astrocytoma using a human recombinant antibody to the extra domain-B of fibronectin
Differentiation between high- and low-grade astrocytoma using a human recombinant antibody to the extra domain-B of fibronectin
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DOI：
10.1016/s0002-9440(10)64446-x
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发表时间：
2002-11-01
影响因子：
6
通讯作者：
Zardi, L
中科院分区：
文献类型：
--
作者：
Castellani, P;Borsi, L;Zardi, L
不同的纤连蛋白（FN）同种型;通过选择性剪接的主要FN转录。我们以前证明，含有纤连蛋白（B-FN）的额外结构域B序列（一个完整的M型同源重复序列）的同种型是血管生成的标志物，仅在血管生成过程中在新血管周围积累。我们制备了一种单链人重组抗体（scFv），L19，它与B-FN特异性反应，并选择性靶向体内肿瘤血管。我们在低级别和高级别星形细胞瘤标本的双重染色程序中使用这种scFv和抗泛内皮标记物（因子VIII）的抗体，以确定B-FN阳性血管的百分比（命名为血管生成指数[AI]）。与血管密度和增殖活性（分别使用因子VIII和Ki 67抗体进行评估）相比，Al与肿瘤分级的相关性更好（低级别和高级别星形细胞瘤中B-FN阳性血管分别为1.6 +/- 2.6%和92.0 +/- 8.7%），并且是比两种传统方法更精确的诊断工具。事实上，使用这三个参数的判别分析表明，只有Al准确地分类了100%的研究病例，而血管密度和增殖细胞的正确诊断率分别为64%和89%。
Different fibronectin (FN) isoforms; are generated by the alternative splicing of the primary FN transcript. We previously demonstrated that the isoform containing the extra domain B sequence of fibronectin (B-FN), a complete type-M-homology repeat, is a marker of angiogenesis that accumulates around neo-vasculature only during angiogenic processes. We produced a single-chain human recombinant antibody (scFv), L19, which reacts specifically with B-FN and selectively targets tumor vasculature in vivo. We used this scFv and an antibody against a pan-endothelial marker (Factor VIII) in a double-staining procedure on specimens of low- and high-grade astrocytomas to determine the percentage of B-FN-positive vessels, (denominating the resulting value angiogenic index [AI]). Compared to vascular density and proliferative activity (evaluated using antibodies to Factor VIII and Ki67, respectively), Al correlated better with tumor grade (1.6 +/- 2.6% and 92.0 +/- 8.7% of B-FN-positive vessels in low- and high-grade astrocytomas, respectively) and was a more precise diagnostic tool than either of the two conventional methods. In fact, discriminating analysis using these three parameters showed that only Al accurately classified 100% of the cases studied, compared to 64% and 89% correctly diagnosed by vascular density and of proliferating cells, respectively.