Tumor angiogenesis correlates with metastatic disease, N-myc amplification, and poor outcome in human neuroblastoma

Tumor angiogenesis correlates with metastatic disease, N-myc amplification, and poor outcome in human neuroblastoma
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DOI:
10.1200/jco.1996.14.2.405
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发表时间:
1996-02-01
影响因子:
45.3
通讯作者:
Cohn, SL
Cohn, SL
中科院分区:
医学1区
文献类型:
--
作者:
Meitar, D;Crawford, SE;Cohn, SL

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目的:确定神经母细胞瘤(NB)儿童的临床结果是否与肿瘤新生血管形成程度相关,并评估分期、N-myc 拷贝数和组织学与血管生成的关系。材料和方法:对 1984 年至 1994 年期间在同一机构诊断的 50 名原发性未治疗 NB 患者的血管分布进行评估,使用图像处理器分析每个肿瘤组织学切片的肿瘤组织面积,并通过计算血管指数 (VI),其中 VI = 血管总数/mm(2) 组织面积,根据 Shimada 等人的标准 (J Natl Cancer Inst 73:405-416, 1984) 对肿瘤进行组织学分类,并通过 Southern blot 分析确定 N-myc 拷贝数。 结果:我们发现 NE 中较高的 VI (> 4.0) 与广泛播散的疾病密切相关 (P = .006) 和较差的生存率 (P < .0001)。 VI 超过 4.0 也与 N-myc 扩增 (P = .02) 和不利的组织学 (P = .02) 存在统计学相关性,单变量分析表明疾病分期、肿瘤组织学和 N-myc 拷贝数也可预测结果,Cox 回归分析显示 VI 提供了独立的预后信息。 结论:我们的研究表明血管生成可能在确定 NB 的生物学行为中发挥重要作用。抗血管生成疗法可能被证明对治疗患有高血管性、广泛播散性 NB 的儿童有效。 (C) 1996 年,美国临床肿瘤学会。
Purpose: To determine if the clinical outcome of children with neuroblastoma (NB) is correlated with the degree of tumor neovascularization and to assess the relationship of stage, N-myc copy number, and histology to angiogenesis.Materials and Methods: The vascularity of primary untreated NB from 50 patients diagnosed at a single institution between 1984 and 1994 wets evaluated, An image processor was used to analyze the tumor tissue area for each histologic slide of tumor, and a vascular index (VI) was calculated, where VI = total number of vessels/mm(2) of tissue area, Tumors were classified histologically according to the criteria of Shimada et al (J Natl Cancer Inst 73:405-416, 1984), and N-myc copy number was determined by Southern blot analysis.Results: We found that higher VI (> 4.0) in NE strongly correlated with widely disseminated disease (P = .006) and poor survival (P < .0001). VI more than 4.0 was also statistically associated with N-myc amplification (P = .02) and unfavorable histology (P = .02), Univariate analysis demonstrated that disease stage, tumor histology, and N-myc copy number were also predictive of outcome, Cox regression analysis showed that VI provided independent prognostic information.Conclusion: Our studies indicate that angiogenesis may play an important role in determining the biologic behavior of NB. Antiangiogenic therapy may prove to be effective in the treatment of children with highly vascular, widely disseminated NB. (C) 1996 by American Society of Clinical Oncology.