GENE AMPLIFICATION IN MALIGNANT HUMAN GLIOMAS - CLINICAL AND HISTOPATHOLOGIC ASPECTS
GENE AMPLIFICATION IN MALIGNANT HUMAN GLIOMAS - CLINICAL AND HISTOPATHOLOGIC ASPECTS
复制标题
DOI：
10.1097/00005072-198805000-00001
复制
发表时间：
1988-05-01
影响因子：
3.2
通讯作者：
BIGNER, DD
中科院分区：
文献类型：
--
作者：
BIGNER, SH;BURGER, PC;BIGNER, DD
45-50%的恶性人脑胶质瘤(MHG)存在基因扩增。本研究对具有基因特征的胶质瘤进行评估，以确定具有表皮生长因子受体(EGFR)、N-myc-c-myc或gli基因扩增的肿瘤是否具有明显的组织病理学特征。肿瘤中含有扩增基因的患者与未表现出这一特征的患者在年龄(p=0.10)或性别(p=0.78)上没有显著差异。虽然在肿瘤中有扩增基因的患者比没有检测到基因扩增的患者存活时间略长，但这些差异没有统计学意义(p=0.21)。扩增的28例肿瘤中，多形性胶质母细胞瘤24例(50%)，间变性星形细胞瘤2例(33%)，胶质肉瘤2例(40%)。1例少突胶质细胞瘤、3例间变性混合性胶质瘤和1例多形性巨细胞胶质母细胞瘤均未见扩增。坏死和血管内皮细胞增殖在有扩增和无扩增的肿瘤中同样普遍。比较有基因扩增的肿瘤和没有这种特征的肿瘤，发现大多数形态细胞类型的分布相似。尽管在未扩增的肿瘤中，显著的血管周围淋巴细胞渗入更为常见，但这种关联在统计学上具有边缘意义。使用EGFR mRNA探针对肿瘤进行扩增的原位杂交显示，不同类型的肿瘤细胞包括纤维状和原浆星形胶质细胞、双生细胞、间变性细胞和多核巨细胞被强烈标记。肿瘤内的非肿瘤细胞，如增生的内皮细胞，不表达可检测到的EGFR mRNA。这些研究表明：(A)同一肿瘤内具有完全不同形态的细胞可能包含相同的基因改变；(B)具有相同组织形态的肿瘤可能是由不同的分子机制产生和进化的；以及(C)分子分析对于评估MHG的基因扩增是必要的，因为这一特征不能通过本研究中使用的形态或临床标准来准确预测。
Gene amplification occurs in 45-50% of malignant human gliomas (MHG). In the present study, 64 genetically characterized gliomas were evaluated to determine if tumours with amplification of the epidermal growth factor receptor (EGFR), N-myc-c-myc, or gli genes had distinctive histopathologic features. There was no significant difference in age (p = 0.10) or gender (p = 0.78) between patients whose tumors contained amplified genes and those whose tumors did not exhibit this characteristic. Although the patients with amplified genes in their tumors survived slightly longer than patients whose tumors had no detectable gene amplification, these differences were not statistically significant (p = 0.21). The 28 tumors with amplification included 24/48 (50%) glioblastoma multiforme, 2/6 (33%) anaplastic astrocytomas and 2/5 (40%) gliosarcomas. No amplification was seen in one oligodendroglioma, three anaplastic mixed gliomas or one giant cell glioblastoma multiforme. Necrosis and endothelial proliferation were equally prevalent among tumors with and without amplification. Comparison of tumors with gene amplification and tumors without this characteristic revealed similar distributions of most morphologic cell types. Although prominent perivascular lymphocytic infiltrates were more frequent in tumors without amplification, this association was of borderline significance statistically. In situ hybridization of tumors with amplification using an EGFR mRNA probe showed intense labeling of different neoplastic cell types including fibrillary and protoplasmic astrocytes, gemistocytes, anaplastic cells, and multinucleated giant cells. Non-neoplastic cells such as hyperplastic endothelium within the tumors did not express detectable EGFR mRNA. These studies demonstrate that (a) cells with quite different morphology within the same tumor can contain the same genetic alteration; (b) tumors of identical histological appearance may have arisen and evolved by different molecular mechanisms; and (c) molecular analyses are necessary to evaluate gene amplification in MHG since this characteristic cannot be accurately predicted by the morphologic or clinical criteria used in this study.