Expression of p53 and prognosis in children with malignant gliomas
Expression of p53 and prognosis in children with malignant gliomas
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DOI：
10.1056/nejmoa012224
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发表时间：
2002-02-07
影响因子：
158.5
通讯作者：
Sposto, R
中科院分区：
文献类型：
--
作者：
Pollack, IF;Finkelstein, SD;Sposto, R
背景：即使考虑到临床和组织学表现，儿童高级别胶质瘤的预后仍不确定。我们研究了高级别胶质瘤中TP 53基因突变或p53蛋白表达程度是否与这些肿瘤儿童的无进展生存期相关。方法：通过TP 53突变分析评估了在儿童癌症组研究CCG-945中接受治疗的儿童恶性胶质瘤的石蜡包埋标本，p53蛋白免疫组化分析115例。对于突变研究，通过显微切割分离含有恶性胶质瘤的组织区域，并对DNA进行基于聚合酶链式反应的扩增和TP 53外显子5、6、7和8的测序。采用微波增强抗原修复法和结合野生型和突变型p53的抗体进行免疫组化分析。结果：我们发现p53过表达与预后显著相关;这种相关性与组织学特征、年龄、性别、切除程度和肿瘤位置无关。p53低表达组74例患者的5年无进展生存率（+/-SE）为44+/-6%，p53过表达组41例患者的5年无进展生存率（+/-SE）为17+/-6%（P
Background: The prognosis of children with high-grade gliomas is uncertain, even when clinical and histologic findings are considered. We investigated whether mutations in the TP53 gene or the degree of expression of p53 protein in high-grade gliomas is associated with progression-free survival in children with these tumors.Methods: Paraffin-embedded specimens of malignant gliomas from children treated in the Children's Cancer Group study CCG-945 were assessed by mutational analysis of TP53 (121 specimens) and immunohistochemical analysis of p53 (115 specimens). For mutational studies, areas of tissue that contained malignant glioma were isolated by microdissection, and the DNA was subjected to polymerase-chain-reaction-based amplification and sequencing of TP53 exons 5, 6, 7, and 8. Immunohistochemical analysis was performed with the use of a microwave-enhanced antigen retrieval and an antibody that bound both wild-type and mutant p53.Results: We found a significant association between overexpression of p53 and outcome; this association was independent of histologic features, age, sex, the extent of resection, and tumor location. The rate (+/-SE) of progression-free survival at five years was 44+/-6 percent in the group of 74 patients whose tumors had low levels of expression of p53 and 17+/-6 percent in the group of 41 patients whose tumors had overexpression of p53 (P