Department of Pathology, University of Valencia, Valencia, Spain.
Neuropathology. 2010 Aug;30(4):392-400. doi: 10.1111/j.1440-1789.2009.01081.x. Epub 2009 Dec 16.
Glioblastomas express a notable heterogeneity in both the histological and cell patterns with glial astrocytic differentiation. Primary glioblastoma, which is the most frequent presentation (90-95%), occurs mainly in older patients and arises de novo, without any clinical or histological evidence of a less malignant precursor lesion. EGFR amplification has been identified as a genetic hallmark of primary glioblastomas and occurs in 40-60% of cases. However, there exist primary glioblastomas without EGFR amplification/overexpression. The purpose of this study was to stabilize the association between cases with and without EGFR gene amplification with clinical and genetic parameters in 45 cases of primary glioblastomas. EGFR amplification was observed in 24 cases (53%), while in the remaining 21 cases (47%) this alteration was not displayed. And whereas EGFR was overexpressed in 79% of cases with EGFR amplification, only 33% of the cases without EGFR amplification showed overexpression. The amplification of EGFR was associated with amplifications in MDM2 and CDK4 and a higher percentage of cases with promoter methylation of INK4a. Only one case of glioblastoma with EGFR amplification presented TP53 mutation simultaneously. Seven remaining cases with TP53 mutations were glioblastomas without EGFR amplification. The INK4a, INK4b and ARF deletions were similar in the two groups. Primary glioblastomas with and without EGFR amplification did not show any significant differences in average survival. The genetic studies suggest the existence of molecular subtypes within primary glioblastoma that may, when fully defined, contribute toward the development of drugs that specifically target tumors with divergent genetic profiles.
胶质母细胞瘤在组织学和细胞形态上表现出明显的异质性，具有神经胶质星形细胞分化。原发性胶质母细胞瘤是最常见的表现形式（90-95%），主要发生在老年患者中，是从头发生的，没有任何临床或组织学证据表明存在恶性程度较低的前体病变。EGFR 扩增已被确定为原发性胶质母细胞瘤的遗传标志，发生在 40-60%的病例中。然而，也存在没有 EGFR 扩增/过表达的原发性胶质母细胞瘤。本研究的目的是在 45 例原发性胶质母细胞瘤中，将有和没有 EGFR 基因扩增的病例与临床和遗传参数稳定关联。在 24 例（53%）病例中观察到 EGFR 扩增，而在其余 21 例（47%）病例中未显示这种改变。在 EGFR 扩增的病例中，EGFR 过表达率为 79%，而在没有 EGFR 扩增的病例中，只有 33%显示过表达。EGFR 扩增与 MDM2 和 CDK4 的扩增以及 INK4a 启动子甲基化的病例百分比较高相关。仅有 1 例 EGFR 扩增的胶质母细胞瘤同时存在 TP53 突变。其余 7 例存在 TP53 突变的病例为无 EGFR 扩增的胶质母细胞瘤。INK4a、INK4b 和 ARF 的缺失在两组中相似。有和没有 EGFR 扩增的原发性胶质母细胞瘤在平均生存时间上没有显示出任何显著差异。遗传研究表明，原发性胶质母细胞瘤中存在分子亚型，当完全定义时，可能有助于开发针对具有不同遗传特征的肿瘤的特异性药物。
