Combined histopathological and molecular cytogenetic stratification of medulloblastoma patients
Combined histopathological and molecular cytogenetic stratification of medulloblastoma patients
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DOI：
10.1158/1078-0432.ccr-03-0721
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发表时间：
2004-08-15
影响因子：
11.5
通讯作者：
Ellison, DW
中科院分区：
文献类型：
--
作者：
Lamont, JM;McManamy, CS;Ellison, DW
本研究通过精细的组织病理学分类和分子细胞遗传学评估的结合来检查对患有髓母细胞瘤的儿童进行分层的效用。来自主要由进入国际儿科肿瘤学会（SIOP）/英国儿童癌症研究组PNET 3试验（n = 65）的儿童组成的一组患者（n = 87）的肿瘤的详细组织病理学分类，包括鉴定大细胞/间变性表型。荧光原位杂交检测17号染色体异常、9 q22和10 q24缺失、MYCC和MYCN癌基因扩增，20%的髓母细胞瘤中存在大细胞/间变性表型，这是一个独立的预后指标。17p13.3缺失（38%的髓母细胞瘤）在所有的组织病理学变异中发现，而MYCC/MYCN扩增（6%/8%的髓母细胞瘤）与大细胞/间变性表型显著相关。这两种遗传异常都是预后指标。9 q22的缺失与结节性/促结缔组织增生性髓母细胞瘤变异相关，而10 q24的缺失在所有变异中均被发现。与表现时的转移性肿瘤一起，大细胞/间变性表型，17p13.3丢失，或高频率MYC扩增定义了一个高危儿童组，其结果是显著的，（P = 0.0002）比没有这些肿瘤特征的低风险组差。新的组织病理学特征和分子细胞遗传学异常的联合评估有望使髓母细胞瘤患者分层，这样那些有可能被治愈的人就不会受到针对侵袭性疾病的最大治疗的副作用。
This study examined the utility of stratifying children with medulloblastomas by a combination of refined histopathological classification and molecular cytogenetic evaluation.Detailed histopathological classification of tumors from a cohort of patients (n = 87) composed mainly of children entered into the International Society of Pediatric Oncology (SIOP)/United Kingdom Children's Cancer Study Group PNET3 trial (n = 65), included identification of the large cell/anaplastic phenotype. Fluorescence in situ hybridization was used to detect chromosome 17 abnormalities, losses of 9q22 and 10q24, and amplification of the MYCC and MYCN oncogenes.The large cell/anaplastic phenotype, which was present in 20% of medulloblastomas, emerged as an independent prognostic indicator. Loss of 17p13.3 (38% of medulloblastomas) was found across all of the histopathological variants, whereas MYCC/MYCN amplification (6%/8% of medulloblastomas) was significantly associated with the large cell/ anaplastic phenotype. Both of these genetic abnormalities emerged as prognostic indicators. Loss of 9q22 was associated with the nodular/desmoplastic medulloblastoma variant, whereas loss of 10q24 was found in all of the variants. Together with metastatic tumor at presentation, the large cell/anaplastic phenotype, 17p13.3 loss, or high-frequency MYC amplification defined a high-risk group of children whose outcome was significantly (P = 0.0002) poorer than a low-risk group without these tumor characteristics.Combined evaluation of novel histopathological features and molecular cytogenetic abnormalities promises to allow stratification of patients with medulloblastoma, such that those likely to be cured will be spared the side effects of maximal therapy, which can be targeted at those with aggressive disease.