Protein overexpression and gene amplification of epidermal growth factor receptor in nonsmall cell lung carcinomas: Comparison of four commercially available antibodies by immunohistochemistry and fluorescence in situ hybridization study
Protein overexpression and gene amplification of epidermal growth factor receptor in nonsmall cell lung carcinomas: Comparison of four commercially available antibodies by immunohistochemistry and fluorescence in situ hybridization study
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DOI：
10.1016/j.lungcan.2009.07.014
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发表时间：
2010-06-01
期刊：
影响因子：
5.3
通讯作者：
Chung, Jin-Haeng
中科院分区：
文献类型：
--
作者：
Lee, Hyun Ju;Xu, Xianhua;Chung, Jin-Haeng
表皮生长因子受体（EGFR）过度表达在非小细胞肺癌（NSCLC）中的变化范围为19%至89%，其预后价值仍存在争议。我们试图研究（1）EGFR蛋白表达使用四种不同的抗体，（2）蛋白过表达和EGFR基因扩增之间的相关性，（3）EGFR基因状态和临床病理特征之间的相关性在NSCLC。我们使用四种不同的抗体，包括Zymed EGFR试剂盒（克隆31 G7）、Dako EGFR pharmDx试剂盒（克隆2- 18 C9）、Dako（克隆H11）和Novocastra（克隆EGFR 113），通过免疫组织化学分析检测EGFR蛋白表达。通过荧光原位杂交（FISH）将蛋白质过表达与基因扩增状态进行比较。使用Zymed EGFR试剂盒、Dako EGFR pharmDx试剂盒、Dako和Novocastra分别在56%、51%、5%和18%的肿瘤中观察到EGFR蛋白过表达（p = 0.010）。Zymed和Dako pharmDx试剂盒的灵敏度均高于Dako检测试剂盒（克隆H11）和Novocastra克隆EGFR 113。EGFR过表达在鳞状细胞癌（SCC）中比腺癌（ADC）中更显著（Zymed组为71% vs. 48%，p = 0.001; Dako pharmDx试剂盒组为61% vs. 45%，p = 0.011）。在45%的NSCLC患者中观察到EGFR FISH阳性，表现为高度多体性和基因扩增。蛋白质表达水平与每个肿瘤细胞的基因拷贝数显著相关（p < 0.001）。我们的数据显示，Zymed和Dako pharmDx检测试剂盒检出的阳性细胞百分比较高。EGFR蛋白过表达率在4%~ 72%之间，随抗体克隆和组织学类型的不同而不同。Zymecl和Dako pharmDx检测到的EGFR蛋白表达与高EGFR基因拷贝数显著相关。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
Epidermal growth factor receptor (EGFR) overexpression in nonsmall cell lung carcinomas (NSCLC) is variable ranging from 19% to 89% and its prognostic value remains controversial. We tried to investigate (1) EGFR protein expression using four different antibodies, (2) the correlation between protein overexpression and EGFR gene amplification, and (3) the correlation between EGFR genetic status and clinicopathologic features in NSCLC. We examined EGFR protein expression using four different antibodies including Zymed EGFR kit (Clone 31G7), Dako EGFR pharmDx kit (Clone 2-18C9), Dako (Clone H11) and Novocastra (Clone EGFR 113) by immunohistochemical analysis. The protein overexpression was compared to gene amplification status by fluorescence in situ hybridization (FISH). EGFR protein overexpression was observed in 56% of tumors with Zymed EGFR kit, in 51% with Dako EGFR pharmDx kit, in 5% with Dako and in 18% with Novocastra (p = 0.010). Both Zymed and Dako pharmDx kit were more sensitive than the Dako test (clone H11) and Novocastra clone EGFR 113. EGFR overexpression was more prominent in squamous cell carcinomas (SCC) than adenocarcinomas (ADC) (71% vs. 48%, p = 0.001 with Zymed, 61% vs. 45%, p = 0.011 with Dako pharmDx kit; respectively). EGFR FISH-positivity as represented by high polysomy and gene amplification was observed in 45% of the NSCLC patients. Protein expression levels significantly correlated with the gene copy number per tumor cell (p < 0.001). Our data showed a higher percentage of positive cells detected by Zymed and Dako pharmDx tests. The EGFR protein overexpression rate varied from 4% to 72% according to different antibody clones and histologic types. EGFR protein expression detected by Zymecl and Dako pharmDx was significantly associated with a high EGFR gene copy number. (C) 2009 Elsevier Ireland Ltd. All rights reserved.