Caron H, van Sluis P, de Kraker J, Bökkerink J, Egeler M, Laureys G, Slater R, Westerveld A, Voûte P A, Versteeg R
Department of Pediatric Oncology and Hematology, Emma Kinderziekenhuis-Academic Medical Center, Amsterdam, The Netherlands.
N Engl J Med. 1996 Jan 25;334(4):225-30. doi: 10.1056/NEJM199601253340404.
Neuroblastoma is a childhood tumor derived from cells of the neural crest, with a widely variable outcome. Differences in the behavior and prognosis of the tumor suggest that neuroblastoma can be divided into several biologic subgroups. We evaluated the most frequent genetic abnormalities in neuroblastoma to determine their prognostic value.
We used Southern blot analysis to study the allelic loss of chromosomes 1p, 4p, 11q, and 14q, the duplication of chromosome 17q, and the amplification of the N-myc oncogene in 89 neuroblastomas. We also determined the nuclear DNA content of the tumor cells.
Allelic loss of chromosome 1p, N-myc amplification, and extra copies of chromosome 17q were significantly associated with unfavorable outcome. In a multivariate analysis, loss of chromosome 1p was the most powerful prognostic factor. It provided strong prognostic information when it was included in multivariate models containing the prognostic factors of age and stage or serum ferritin level and stage. Among the patients with stage I, II, or IVS disease, the mean (+/- SD) three-year event-free survival was 100 percent in those without allelic loss of chromosome 1p and 34 +/- 15 percent in those with such loss; the rates of three-year event-free survival among the patients with stage III and stage IV disease were 53 +/- 10 percent and 0 percent, respectively.
The loss of chromosome 1p is a strong prognostic factor in patients with neuroblastoma, independently of age and stage. It reliably identifies patients at high risk in stages I, II, and IVS, which are otherwise clinically favorable. More intensive therapy may be considered in these patients. Patients in stages III and IV with allelic loss of chromosome 1p have a very poor outlook, whereas those without such loss are at moderate risk.
神经母细胞瘤是一种起源于神经嵴细胞的儿童肿瘤，其预后差异很大。肿瘤行为和预后的差异表明神经母细胞瘤可分为几个生物学亚组。我们评估了神经母细胞瘤中最常见的基因异常，以确定它们的预后价值。
我们采用Southern印迹分析法研究了89例神经母细胞瘤中1p、4p、11q和14q染色体的等位基因缺失、17q染色体的重复以及N-myc癌基因的扩增情况。我们还测定了肿瘤细胞的核DNA含量。
1p染色体等位基因缺失、N-myc扩增和17q染色体额外拷贝与不良预后显著相关。在多变量分析中，1p染色体缺失是最有力的预后因素。当将其纳入包含年龄和分期或血清铁蛋白水平和分期等预后因素的多变量模型时，它提供了强有力的预后信息。在Ⅰ、Ⅱ或ⅣS期疾病患者中，无1p染色体等位基因缺失者的平均（±标准差）三年无事件生存率为100%，有该缺失者为34±15%；Ⅲ期和Ⅳ期疾病患者的三年无事件生存率分别为53±10%和0%。
1p染色体缺失是神经母细胞瘤患者的一个强有力的预后因素，与年龄和分期无关。它能可靠地识别出Ⅰ、Ⅱ和ⅣS期临床上原本预后良好但处于高风险的患者。对于这些患者可考虑更强化的治疗。Ⅲ期和Ⅳ期有1p染色体等位基因缺失的患者预后很差，而无此缺失者处于中度风险。
