Amplification of the epidermal growth factor receptor in astrocytic tumours by chromogenic in situ hybridization:: association with clinicopathological features and patient survival
Amplification of the epidermal growth factor receptor in astrocytic tumours by chromogenic in situ hybridization:: association with clinicopathological features and patient survival
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DOI：
10.1111/j.1365-2990.2006.00758.x
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发表时间：
2006-08-01
影响因子：
5
通讯作者：
Isola, J.
中科院分区：
文献类型：
--
作者：
Jarvella, S.;Helin, H.;Isola, J.
显色原位杂交（CISH）用于检测来自287例II-IV级弥漫性星形细胞瘤患者的肿瘤组织微阵列中表皮生长因子受体（EGFR）基因的扩增。在32%的肿瘤中发现扩增，与组织学分级高度显著相关（II级4%，III级21%，IV级39%; P < 0.001）。EGFR基因扩增在原发性胶质母细胞瘤中比在继发性胶质母细胞瘤中更常见（41 vs. 16%，P = 0.033）。EGFR mRNA和蛋白（野生型和vIII变体）的过表达与EGFR基因扩增相关（分别为P = 0.028，P = 0.035和P = 0.014），但野生型EGFR蛋白在无EGFR基因扩增的肿瘤中也经常过表达。年龄越大（P < 0.001）、p53蛋白表达水平越低（P = 0.03）、凋亡率越高（P < 0.001）的患者EGFR基因扩增率越高。在胶质母细胞瘤中没有发现这种与细胞凋亡的相关性。EGFR基因扩增III级肿瘤患者的生存期明显短于III级非扩增肿瘤患者（P = 0.03）。在胶质母细胞瘤（IV级肿瘤）中没有观察到这种差异。我们的数据验证了EGFR在星形细胞肿瘤的病理生物学中的核心作用，并突出了CISH作为一种简单实用的检测星形细胞肿瘤中EGFR基因扩增的筛查方法的优势。
Chromogenic in situ hybridization (CISH) was used to detect amplification of the epidermal growth factor receptor (EGFR) gene in tissue microarrays of tumours derived from 287 patients with grade II-IV diffuse astrocytomas. Amplification was found in 32% of the tumours with a highly significant association with histological grade (4% in grade II, 21% in grade III and 39% in grade IV; P < 0.001). Amplification of the EGFR gene was more common in primary than in secondary glioblastomas (41 vs. 16%, P = 0.033). Overexpression of EGFR mRNA and protein (wild-type and vIII variant) was found to correlate with EGFR gene amplification (P = 0.028, P = 0.035 and P = 0.014 respectively), but wild-type EGFR protein was also frequently overexpressed in tumours without EGFR gene amplification. Patients with older age (P < 0.001) and tumours with lack of p53 overexpression (P = 0.03) and higher apoptosis rate (P < 0.001) had significantly more EGFR gene amplifications than their counterparts. No such correlation with apoptosis was found in glioblastomas. The survival of patients with EGFR gene-amplified grade III tumours was significantly shorter than in those with grade III non-amplified tumours (P = 0.03). No such difference was noted in glioblastomas (grade IV tumours). Our data verify the central role of EGFR in the pathobiology of astrocytic tumours, and highlight the advantages of CISH as a simple and practical assay to screen for EGFR gene amplification in astrocytic tumours.