Novel epidermal growth factor receptor mutation-specific antibodies for non-small cell lung cancer: immunohistochemistry as a possible screening method for epidermal growth factor receptor mutations.
Novel epidermal growth factor receptor mutation-specific antibodies for non-small cell lung cancer: immunohistochemistry as a possible screening method for epidermal growth factor receptor mutations.
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DOI：
10.1097/jto.0b013e3181e9da60
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发表时间：
2010-10
期刊：
影响因子：
--
通讯作者：
Hirsch FR
中科院分区：
文献类型：
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作者：
Kato Y;Peled N;Wynes MW;Yoshida K;Pardo M;Mascaux C;Ohira T;Tsuboi M;Matsubayashi J;Nagao T;Ikeda N;Hirsch FR
非小细胞肺癌（NSCLC）中的表皮生长因子受体（EGFR）突变预测EGFR酪氨酸激酶抑制剂（TKI）的结局更好。最常见的突变是外显子19缺失（最常见的是E746-A750）和外显子21中的L 858 R点突变。在此，我们评估了新型EGFR突变特异性抗体在日本NSCLC队列中的准确性，并与直接DNA测序和临床结果进行了比较。使用EGFR中E746-A750和L 858 R突变特异性抗体对70例吉非替尼治疗的NSCLC患者的肿瘤组织微阵列进行免疫组织化学（IHC）。对提取的DNA进行测序，用于EGFR外显子18至21的突变分析。DNA测序显示41例患者（58.6%）存在EGFR突变，18例患者（25.7%）存在外显子19缺失，61%（11/18）的缺失范围为E746-A750），12例（17.1%）存在外显子21突变（L 858 R）。免疫组化显示，E746-A750和L 858 R突变的敏感性（81.8%和75%），特异性（100%，96.6%），PPV（100%，81.8%）和NPV（96.7%，94.9%）。客观缓解率（ORR）和生存期分析与IHC染色无关，尽管联合染色显示EGFR突变患者的总生存期无显著改善趋势。突变特异性IHC抗体对预定义的EFGR突变具有高灵敏度和特异性，并且可适用于筛选这些预定义的突变。然而，阴性IHC结果需要在排除EGFR靶向治疗之前进行进一步的突变分析。
Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) predict better outcome to EGFR tyrosine kinase inhibitors (TKIs). The most common mutations are exon 19 deletions (most frequently E746-A750) and L858R point mutation in exon 21. Here, we evaluated the accuracy of novel EGFR mutation specific antibodies in a Japanese cohort with NSCLC and compared to direct DNA sequencing and clinical outcome. Immunohistochemistry (IHC) using antibodies specific for the E746-A750 and L858R mutations in EGFR was performed on tissue microarrays of tumors from 70 gefitinib treated NSCLC patients. Extracted DNA was sequenced for mutational analysis of EGFR exons 18 to 21. DNA sequencing showed EGFR mutations in 41 patients (58.6%), and exon 19 deletions in 18 patients (25.7%), 61% (11/18) had a deletion in the range of E746-A750) and 12 (17.1%) had exon 21 mutations (L858R). IHC showed, for the E746-A750 and L858R mutations, sensitivity (81.8% and 75%), specificity (100%, 96.6%), PPV (100%, 81.8%) and NPV (96.7%, 94.9%). Analysis for objective response rates (ORR) and survival were not correlated to IHC staining, although the combined staining showed non-significant trends towards better overall survival for patients with EGFR mutations. The mutation specific IHC antibodies have high sensitivity and specificity for pre-defined EFGR mutations and may be suitable for screening for these pre-defined mutations. However, negative IHC results require further mutation analyses prior to excluding EGFR-targeted therapy.