A rapid, sensitive assay to detect EGFR mutation in small biopsy specimens from lung cancer
A rapid, sensitive assay to detect EGFR mutation in small biopsy specimens from lung cancer
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DOI：
10.2353/jmoldx.2006.050104
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发表时间：
2006-07-01
影响因子：
4.1
通讯作者：
Mitsudomi, Tetsuya
中科院分区：
文献类型：
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作者：
Yatabe, Yasushi;Hida, Toyoaki;Mitsudomi, Tetsuya
已经证明，具有表皮生长因子受体（EGFR）突变的肺癌，特别是肺腺癌的子集，对EGFR靶向药物高度敏感。因此，在临床实践中，需要一种快速、灵敏的检测方法，使用常规病理标本进行突变检测，以预测反应。因此，我们开发了一种新的检测EGFR突变的方法，只使用一个小的活检标本的石蜡切片。该方法非常灵敏，在正常细胞的背景中检测到少至5%的癌细胞，通常在4小时内获得结果。此外，它是准确的，与逆转录酶-聚合酶链反应偶联直接测序（186 195，95%）的高度一致性。该检测方法在29例吉非替尼治疗病例中的实际应用导致了高预测率：11例应答者中有10例显示突变阳性，所有进行性疾病患者均为阴性。此外，在密码子790处的突变，赋予吉非替尼耐药性，成功地以类似的方式进行了分析。总之，该测定是一种快速、灵敏的方法，使用活检标本的石蜡切片，而无需肿瘤细胞富集程序，并且在临床实践中对选择治疗非常有用。
It has been demonstrated that lung cancers, specifically a subset of pulmonary adenocarcinomas, with epidermal growth factor receptor (EGFR) mutation are highly sensitive to EGFR-targeted drugs. Therefore, a rapid, sensitive assay for mutation detection using routine pathological specimens is demanded in clinical practice to predict the response. We therefore developed a new assay for detecting EGFR mutation using only a paraffin section of a small biopsy specimen. The method was very sensitive, detecting as few as 5% cancer cells in a background of normal cells, the results usually being obtained within 4 hours. Furthermore, it was accurate, as shown by the high concordance with reverse transcriptase-polymerase chain reaction-coupled direct sequencing (186 of 195, 95%). The practical application of this assay to 29 cases treated with gefitinib resulted in a high prediction rate: 10 of the 11 responders were shown to be positive for the mutation, and all patients with progressive disease were negative. In addition, a mutation at codon 790, conferring gefitinib resistance, was successfully analyzed in a similar manner. in conclusion, the assay is a rapid, sensitive method using paraffin sections of biopsy specimens without a tumor cell-enrichment procedure and is quite useful to select a treatment of choice in clinical practice.