Horiike Atsushi, Kimura Hideharu, Nishio Kazuto, Ohyanagi Fumiyoshi, Satoh Yukitoshi, Okumura Sakae, Ishikawa Yuichi, Nakagawa Ken, Horai Takeshi, Nishio Makoto
Thoracic Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Chest. 2007 Jun;131(6):1628-34. doi: 10.1378/chest.06-1673.
Somatic mutations of epidermal growth factor receptor (EGFR) are closely associated with an objective response to EGFR tyrosine kinase inhibitors. However, it is difficult to obtain sufficient tumor samples from patients with non-small cell lung cancer (NSCLC), so these diagnoses are often made using cytology procedures alone. The aim of this study was to detect EGFR mutations in transbronchial needle aspiration (TBNA) samples using both direct sequencing and a highly sensitive assay (Scorpions Amplified Refractory Mutation System; DxS; Manchester, UK) [ARMS], and to compare the sensitivity of these methods.
We enrolled 94 patients (63 men and 31 women) with NSCLC in this study. Cytologic diagnoses were adenocarcinoma (n = 58), squamous cell carcinoma (n = 24), and other types of NSCLC (n = 12). We extracted DNA from the TBNA samples, and EGFR mutations were analyzed using both direct sequencing (exons 19 and 21) and the Scorpions ARMS method (E746 A750del and L858R).
Mutations were detected in 31 patients (33%; 14 women and 17 men). Of these, 23 patients had adenocarcinoma, 4 had squamous cell carcinoma, and 4 had other types of NSCLC. Direct sequencing detected 13 mutations (14%) in 13 patients (E746-A750del, n = 6; L858R, n = 7), and the Scorpions ARMS method detected 27 mutations (29%) in 27 patients (E746 A750del, n = 16; L858R, n = 11 patients).
Both methods detected EGFR mutations in TBNA samples, but Scorpions ARMS is more sensitive than direct sequencing.
表皮生长因子受体（EGFR）的体细胞突变与EGFR酪氨酸激酶抑制剂的客观反应密切相关。然而，从非小细胞肺癌（NSCLC）患者中获取足够的肿瘤样本很困难，因此这些诊断通常仅使用细胞学程序进行。本研究的目的是使用直接测序和高灵敏度检测方法（蝎尾引物扩增难治性突变系统；DxS；英国曼彻斯特）[ARMS]检测经支气管针吸活检（TBNA）样本中的EGFR突变，并比较这些方法的灵敏度。
本研究纳入了94例NSCLC患者（63例男性和31例女性）。细胞学诊断为腺癌（n = 58）、鳞状细胞癌（n = 24）和其他类型的NSCLC（n = 12）。我们从TBNA样本中提取DNA，并使用直接测序（外显子19和21）和蝎尾引物ARMS方法（E746 A750del和L858R）分析EGFR突变。
在31例患者（33%；14例女性和17例男性）中检测到突变。其中，23例患者为腺癌，4例为鳞状细胞癌，4例为其他类型的NSCLC。直接测序在13例患者中检测到13个突变（14%）（E746 - A750del，n = 6；L858R，n = 7），蝎尾引物ARMS方法在27例患者中检测到27个突变（29%）（E746 A750del，n = 16；L858R，n = 11例患者）。
两种方法均检测到TBNA样本中的EGFR突变，但蝎尾引物ARMS比直接测序更灵敏。
