Comprehensive Analysis of Epidermal Growth Factor Receptor Gene Status in Lung Adenocarcinoma
Comprehensive Analysis of Epidermal Growth Factor Receptor Gene Status in Lung Adenocarcinoma
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肺腺癌表皮生长因子受体基因状态综合分析
DOI：
10.1097/jto.0b013e318215a4f2
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发表时间：
2011-06-01
影响因子：
20.4
通讯作者：
Chen, Haiquan
中科院分区：
文献类型：
--
作者：
Li, Chenguang;Sun, Yihua;Chen, Haiquan
简介：据报道，表皮生长因子受体（EGFR）基因状态（包括酪氨酸激酶结构域体细胞突变、拷贝数增加和蛋白质过表达）与非小细胞肺癌患者对EGFR酪氨酸激酶抑制剂的反应相关。本研究的目的是阐明激活的EGFR基因的患病率以及突变、拷贝数和蛋白过表达之间的关系。患者和方法：在一组连续的肺腺癌患者中，通过外显子18至21进行聚合酶链反应和直接测序（n = 89）。采用荧光原位杂交（FISH）技术检测89例患者的基因拷贝数，单核苷酸多态性（SNP）芯片6.0检测77例患者的基因拷贝数。免疫组化法检测EGFR蛋白表达。结果如下：59例（66.3%）患者携带EGFR酪氨酸激酶域的体细胞突变，55.1%的患者IHC阳性，44.9%的患者FISH阳性，66.2%的患者显示拷贝数增加。EGFR体细胞突变在女性、从不吸烟者和分化较好的肿瘤中更常见。FISH和SNP array 6.0分析检测到的拷贝数增加与EGFR突变显著相关。结论：中国肺腺癌患者EGFR体细胞突变率明显高于西方国家。然而，我们发现不同种族之间的FISH和IHC阳性率相当。考虑到FISH可能受到肿瘤异质性等因素的影响，SNP array 6.0分析是检测EGFR拷贝数变异的一种很好的替代方法。
Introduction: The epidermal growth factor receptor (EGFR) gene status including tyrosine kinase domain somatic mutations, increased copy number, and protein overexpression are reported to be associated with response to EGFR tyrosine kinase inhibitors in patients with non-small cell lung cancer. The purpose of this study was to elucidate the prevalence of activated EGFR gene and the association between mutation, copy number, and protein overexpression. Patients and Methods: In a cohort of consecutive patients with lung adenocarcinoma, polymerase chain reaction and direct sequencing (n = 89) were conducted through exons 18 to 21. Fluorescence in situ hybridization (FISH) (n = 89) and single-nucleotide polymorphism (SNP) array 6.0 (n = 77) were used to detect the gene copy number. The protein expression of EGFR was detected by standard immunohistochemistry (IHC) (n = 89). Results: Fifty-nine (66.3%) patients harbored somatic mutations of EGFR in tyrosine kinase domain, 55.1% were positive by IHC and 44.9% were positive by FISH, and 66.2% showed gain of copy number according to SNP array 6.0. EGFR somatic mutations are more common in women, never smokers, and tumors with better differentiation. Increased copy number detected by both FISH and SNP array 6.0 analysis is significantly correlated with mutations of EGFR. Conclusions: The EGFR somatic mutation rate is significantly higher in Chinese patients with lung adenocarcinoma than western countries. Nevertheless, we found comparable FISH and IHC-positive rates between different ethnics. Considering that FISH may be affected by tumor heterogeneity and other factors, SNP array 6.0 analysis is a good alternative method to detect EGFR copy number variations.