The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers.
The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers.
复制标题
DOI：
--
复制
发表时间：
2005-02
期刊：
影响因子：
--
通讯作者：
Masaki Tokumo;S. Toyooka;K. Kiura;H. Shigematsu;K. Tomii;M. Aoe;K. Ichimura;T. Tsuda;M. Yano
中科院分区：
文献类型：
--
作者：
Masaki Tokumo;S. Toyooka;K. Kiura;H. Shigematsu;K. Tomii;M. Aoe;K. Ichimura;T. Tsuda;M. Yano
目的最近的研究报道，吉非替尼的临床反应与非小细胞肺癌（NSCLC）中表皮生长因子受体（EGFR）基因的体细胞突变有关。在这里，我们研究了 EGFR 突变与临床病理特征之间的关系。实验设计 120 例 NSCLC 的 EGFR 突变状态主要通过直接测序确定 EGFR 外显子 18 至 21，并与临床病理参数相关。结果 38例（32%）存在EGFR突变，大多数突变为外显子19的框内缺失（19例）和外显子21的错义突变（18例）。 EGFR 突变经常与腺癌 (P < 0.0001)、从不吸烟者 (P < 0.0001) 和女性 (P = 0.0001) 相关。有趣的是，增加烟雾暴露与 EGFR 突变率呈负相关（P < 0.0001）。多变量分析显示吸烟和组织学是自变量。此外，男性外显子 19 和女性外显子 21 的突变位置优势存在性别差异 (P = 0.01)。 21例接受吉非替尼治疗，发现EGFR突变与吉非替尼反应显着相关（P=0.002）。此外，接受吉非替尼治疗的携带和不携带 EGFR 突变的患者的中位生存时间分别为 25.1 个月和 14.0 个月。 EGFR 突变患者的生存优势约为 2 倍；然而，差异并不显着。结论 我们发现 EGFR 突变与组织学和烟雾暴露显着相关，并且是 NSCLC 吉非替尼反应性的强预测因素。
PURPOSE Recent studies reported that clinical responsiveness to gefitinib was associated with somatic mutation of epidermal growth factor receptor (EGFR) gene in non-small cell lung cancers (NSCLC). Here, we investigated the relationship between EGFR mutation and clinicopathologic features. EXPERIMENTAL DESIGN EGFR mutational status of 120 NSCLCs was determined mainly in EGFR exons 18 to 21 by direct sequence and correlated with clinicopathologic parameters. RESULTS EGFR mutations were present in 38 cases (32%) and the majority of mutations were in-frame deletions of exon 19 (19 cases) and a missense mutation in exon 21 (18 cases). EGFR mutations were frequently associated with adenocarcinoma (P < 0.0001), never smoker (P < 0.0001), and female gender (P = 0.0001). Of interest, increasing smoke exposure was inversely related to the rate of EGFR mutation (P < 0.0001). Multivariate analysis showed that smoking and histology were independent variables. Furthermore, gender difference was observed for the mutational location (P = 0.01) dominance of exon 19 for males and exon 21 for females. Twenty-one cases were treated with gefitinib and found that EGFR mutation was significantly related to gefitinib responsiveness (P = 0.002). In addition, median survival times of patients with and without EGFR mutations treated with gefitinib were 25.1 and 14.0 months, respectively. Patients with EGFR mutations had approximately 2-fold survival advantage; however, the difference was not significant. CONCLUSIONS We show that EGFR mutations were significantly related to histology and smoke exposure and were a strong predictive factor for gefitinib responsiveness in NSCLC.