Takano Toshimi, Ohe Yuichiro, Tsuta Koji, Fukui Tomoya, Sakamoto Hiromi, Yoshida Teruhiko, Tateishi Ukihide, Nokihara Hiroshi, Yamamoto Noboru, Sekine Ikuo, Kunitoh Hideo, Matsuno Yoshihiro, Furuta Koh, Tamura Tomohide
Division of Internal Medicine, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5385-90. doi: 10.1158/1078-0432.CCR-07-0627.
Epidermal growth factor receptor (EGFR) mutations, especially deletional mutations in exon 19 (DEL) and L858R, predict gefitinib sensitivity in patients with non-small cell lung cancer (NSCLC). In this study, we validated EGFR mutation detection using high-resolution melting analysis (HRMA) and evaluated the associations between EGFR mutations and clinical outcomes in advanced NSCLC patients treated with gefitinib on a larger scale.
The presence of DEL or L858R was evaluated using HRMA and paraffin-embedded tissues and/or cytologic slides from 212 patients. In 66 patients, the results were compared with direct sequencing data.
HRMA using formalin-fixed tissues had a 92% sensitivity and a 100% specificity. The analysis was successfully completed in 207 patients, and DEL or L858R mutations were detected in 85 (41%) patients. The response rate (78% versus 8%), time-to-progression (median, 9.2 versus 1.6 months), and overall survival (median, 21.7 versus 8.7 months) were significantly better in patients with EGFR mutations (P < 0.001). Even among the 34 patients with stable diseases, the time-to-progression was significantly longer in patients with EGFR mutations. Patients with DEL (n = 49) tended to have better outcomes than those with L858R (n = 36); the response rates were 86% and 67%, respectively (P = 0.037), and the median time-to-progression was 10.5 and 7.4 months, respectively (P = 0.11).
HRMA is a precise method for detecting DEL and L858R mutations and is useful for predicting clinical outcomes in patients with advanced NSCLC treated with gefitinib.
表皮生长因子受体（EGFR）突变，尤其是外显子19缺失突变（DEL）和L858R突变，可预测非小细胞肺癌（NSCLC）患者对吉非替尼的敏感性。在本研究中，我们验证了使用高分辨率熔解分析（HRMA）检测EGFR突变，并在更大规模上评估了接受吉非替尼治疗的晚期NSCLC患者中EGFR突变与临床结局之间的关联。
使用HRMA对212例患者的石蜡包埋组织和/或细胞学涂片进行DEL或L858R检测。对66例患者的结果与直接测序数据进行比较。
使用福尔马林固定组织进行HRMA的敏感性为92%，特异性为100%。207例患者的分析成功完成，85例（41%）患者检测到DEL或L858R突变。EGFR突变患者的缓解率（78%对8%）、疾病进展时间（中位数，9.2个月对1.6个月）和总生存期（中位数，21.7个月对8.7个月）显著更好（P<0.001）。即使在34例病情稳定的患者中，EGFR突变患者的疾病进展时间也显著更长。DEL患者（n=49）的结局往往比L858R患者（n=36）更好；缓解率分别为86%和67%（P=0.037），疾病进展时间中位数分别为10.5个月和7.4个月（P=0.11）。
HRMA是检测DEL和L858R突变的精确方法，有助于预测接受吉非替尼治疗的晚期NSCLC患者的临床结局。
