Comparison of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell lung cancer
Comparison of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell lung cancer
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DOI：
10.1093/annonc/mdn679
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发表时间：
2009-04-01
影响因子：
50.5
通讯作者：
Shih, J. -Y.
中科院分区：
文献类型：
--
作者：
Gow, C. -H.;Chang, Y. -L.;Shih, J. -Y.
背景资料：非小细胞肺癌（NSCLC）患者表皮生长因子受体（EGFR）基因突变可预测EGFR酪氨酸激酶抑制剂（TKI）治疗的疗效。最近的一项研究表明，33%的NSCLC通过免疫组织化学分析显示原发肿瘤/转移灶EGFR表达不一致。为了解原发性肺癌EGFR突变与相应转移性肿瘤EGFR突变是否一致，材料与方法：我们分析了67例原发性肺癌和转移性肺癌患者的EGFR外显子18-21，这些患者在组织取样前未接受TKI治疗。使用直接测序法，18例EGFR突变阳性原发性肺肿瘤患者中有9例（50%）在转移灶中丢失了突变。在转移性肿瘤中EGFR突变阳性的26例患者中，17例（65%）在原发性肿瘤中为阴性。我们通过Scorpion扩增难治性突变系统分析了这些EGFR突变不一致的配对组织。结论：原发性肺癌EGFR突变并不总是反映转移性肺癌EGFR突变的情况。分析原发性肺肿瘤中的EGFR突变不足以计划TKI在晚期NSCLC中的使用。
Background: Mutations of the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients predict the patients who will respond to EGFR tyrosine kinase inhibitor (TKI) treatment. A recent study has suggested that 33% of NSCLC showed primary tumor/metastasis discordance of EGFR expression by immunohistochemistry analysis. We intended to find out whether the EGFR mutations of primary lung cancers are concordant to that of corresponding metastatic tumors.Materials and methods: We analyzed EGFR exons 18-21 from paired primary and metastatic tumors in 67 lung cancer patients who had not received TKI before tissues were sampled.Results: Using the direct sequencing method, 9 of 18 (50%) patients with EGFR mutation-positive primary lung tumors had lost the mutations in metastases. For 26 patients who were EGFR mutation positive in the metastatic tumors, 17 (65%) were negative in the primary tumors. We analyzed these paired tissues with discrepant EGFR mutations by the Scorpion Amplified Refractory Mutation System assay. Finally, the discordant rate reached 27% (18 of 67 cases).Conclusion: EGFR mutations in primary lung tumors do not always reflect the same situation in metastases. Analysis of EGFR mutations in the primary lung tumor would be inadequate for planning the use of TKI for advanced NSCLC.