非小细胞肺癌（NSCLC）中 EGFR 和 KRAS 突变的频率：来自一项队列研究的中欧常规筛查数据。
The frequency of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC): routine screening data for central Europe from a cohort study.
机构信息
Klinik für Pneumologie, Lungenklinik Heckeshorn, HELIOS Klinikum Emil von Behring, Berlin, Berlin, Germany.
出版信息
BMJ Open. 2013 Apr 3;3(4). doi: 10.1136/bmjopen-2013-002560. Print 2013.
OBJECTIVES
Owing to novel therapy strategies in epidermal growth factor receptor (EGFR)-mutated patients, molecular analysis of the EGFR and KRAS genome has become crucial for routine diagnostics. Till date these data have been derived mostly from clinical trials, and thus collected in pre-selected populations. We therefore screened 'allcomers' with a newly diagnosed non-small cell lung carcinoma (NSCLC) for the frequencies of these mutations.
DESIGN
A cohort study.
SETTING
Lung cancer centre in a tertiary care hospital.
PARTICIPANTS
Within 15 months, a total of 552 cases with NSCLC were eligible for analysis.
PRIMARY AND SECONDARY OUTCOME MEASURES
Frequency of scrutinising exons 18, 19 and 21 for the presence of activating EGFR mutation and secondary codon 12 and 13 for activating KRAS mutations.
RESULTS
Of the 552 patients, 27 (4.9%) showed a mutation of EGFR. 19 of these patients (70%) had deletion E746-A750 in codon 19 or deletion L858R in codon 21. Adenocarcinoma (ACA) was the most frequent histology among patients with EGFR mutations (ACA, 22/254 (8.7%) vs non-ACA, 5/298 (1.7%); p<0.001). Regarding only ACA, the percentage of EGFR mutations was higher in women (16/116 (14%) women vs 6/138 (4.3%) men; p=0.008). Tumours with an activating EGFR mutation were more likely to be from non-smokers (18/27; 67%) rather than smoker (9/27; 33%). KRAS mutation was present in 85 (15%) of all cases. In 73 patients (86%), the mutation was found in exon 12 and in 12 cases (14%) in exon 13. Similarly, ACA had a higher frequency of KRAS mutations than non-ACA (67/254 (26%) vs 18/298 (6.0%); p<0.001).
CONCLUSIONS
We found a lower frequency for EGFR and KRAS mutations in an unselected Caucasian patient cohort as previously published. Taking our results into account, clinical trials may overestimate the mutation frequency for EGFR and KRAS in NSCLC due to important selection biases.
目的
由于表皮生长因子受体（EGFR）突变患者的新型治疗策略，EGFR 和 KRAS 基因组的分子分析已成为常规诊断的关键。迄今为止，这些数据主要来自临床试验，因此是在预先选择的人群中收集的。因此，我们筛选了新诊断的非小细胞肺癌（NSCLC）的“所有患者”，以检测这些突变的频率。
设计
队列研究。
地点
三级护理医院的肺癌中心。
参与者
在 15 个月内，共有 552 例 NSCLC 患者符合分析条件。
主要和次要观察指标
分析外显子 18、19 和 21 中是否存在激活的 EGFR 突变，以及第 12 和 13 密码子中是否存在激活的 KRAS 突变。
结果
在 552 例患者中，有 27 例（4.9%）显示 EGFR 突变。在这 27 例患者中，19 例（70%）在 19 号外显子中存在 E746-A750 缺失或在 21 号外显子中存在 L858R 缺失。腺癌（ACA）是 EGFR 突变患者中最常见的组织学类型（ACA，22/254（8.7%）vs 非 ACA，5/298（1.7%）；p<0.001）。仅在 ACA 中，女性中 EGFR 突变的比例更高（16/116（14%）女性 vs 138（4.3%）男性；p=0.008）。具有激活 EGFR 突变的肿瘤更可能来自非吸烟者（18/27；67%）而不是吸烟者（9/27；33%）。所有病例中有 85 例（15%）存在 KRAS 突变。在 73 例患者（86%）中，突变发生在外显子 12 中，在 12 例患者（14%）中发生在外显子 13 中。同样，ACA 比非 ACA 更频繁地出现 KRAS 突变（67/254（26%）vs 18/298（6.0%）；p<0.001）。
结论
我们在未经选择的白种人群队列中发现 EGFR 和 KRAS 突变的频率较低，这与之前的研究结果一致。考虑到我们的结果，临床试验可能会由于重要的选择偏倚而高估 NSCLC 中 EGFR 和 KRAS 的突变频率。
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