Okami Jiro, Taniguchi Kazuya, Higashiyama Masahiko, Maeda Jun, Oda Kazuyuki, Orita Naoki, Koizumi Kyoko, Kodama Ken, Kato Kikuya
Department of Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
Oncology. 2007;72(3-4):234-42. doi: 10.1159/000112947. Epub 2008 Jan 7.
The association between epidermal growth factor receptor (EGFR) mutations and response to EGFR tyrosine kinase inhibitor (TKI) has been consistently confirmed in a number of studies. However, it is still unclear whether a response to TKI treatment translates into increased survival for patients with non-small cell lung cancer (NSCLC).
EGFR mutations were analyzed in 169 primary lung cancer tissues by RT-PCR and sequencing of multiple clones. The association between EGFR mutation status and the clinical outcome of gefitinib treatment was investigated. For mutation-positive cases, the percentage of mutated clones from the total number of clones was calculated. This ratio was used as the quantitative index of EGFR mutations.
We identified mutations in 71 of 169 patients with NSCLC. 46 patients were treated with gefitinib for postoperative recurrence. Progression-free survival and overall survival after initial gefitinib were significantly longer in patients with mutation than with wild type (univariate analysis, p < 0.001 for both). Multivariate analyses identified EGFR mutations and longer disease-free intervals after surgery as significant prognostic factors for survival. By quantitative analysis of mutation-positive cases, the increased ratio of mutated EGFR transcripts significantly associated with longer survival after gefitinib.
EGFR mutation status and disease-free interval were associated with prolonged progression-free survival and overall survival after gefitinib treatment for postoperative recurrence of NSCLC. Quantitative analysis of mutated EGFR transcripts provided additional information for the stratification of patients with mutated EGFR.
多项研究一致证实表皮生长因子受体（EGFR）突变与EGFR酪氨酸激酶抑制剂（TKI）反应之间的关联。然而，对于非小细胞肺癌（NSCLC）患者，TKI治疗的反应是否转化为生存期延长仍不清楚。
通过RT-PCR和多个克隆测序对169例原发性肺癌组织中的EGFR突变进行分析。研究EGFR突变状态与吉非替尼治疗临床结果之间的关联。对于突变阳性病例，计算突变克隆占克隆总数的百分比。该比率用作EGFR突变的定量指标。
我们在169例NSCLC患者中的71例中鉴定出突变。46例患者接受吉非替尼治疗术后复发。初始使用吉非替尼后，突变患者的无进展生存期和总生存期明显长于野生型患者（单因素分析，两者p均<0.001）。多因素分析确定EGFR突变和术后更长的无病间期是生存的重要预后因素。通过对突变阳性病例的定量分析，突变的EGFR转录本增加比率与吉非替尼治疗后更长的生存期显著相关。
EGFR突变状态和无病间期与NSCLC术后复发吉非替尼治疗后的无进展生存期和总生存期延长相关。突变的EGFR转录本的定量分析为EGFR突变患者的分层提供了额外信息。
