中国非小细胞肺癌患者中表皮生长因子受体（EGFR）和 Kirsten 大鼠肉瘤病毒癌基因（KRAS）突变与预后的关系：使用蝎形扩增不应性突变系统的实时聚合酶链反应突变分析

[Relationship between EGFR and KRAS mutations and prognosis in Chinese patients with non-small cell lung cancer: a mutation analysis with real-time polymerase chain reaction using scorpion amplification refractory mutation system].

作者信息

Gao Jie, Chen Jia-qi, Zhang Li, Liang Zhi-yong

机构信息

Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.

出版信息

Zhonghua Bing Li Xue Za Zhi. 2012 Oct;41(10):652-6. doi: 10.3760/cma.j.issn.0529-5807.2012.10.002.

DOI:10.3760/cma.j.issn.0529-5807.2012.10.002

PMID:23302304

Abstract

OBJECTIVE

To investigate the gene mutation of EGFR and KRAS in Chinese patients with non-small cell lung cancer (NSCLC), and to analyze the relationship between the gene mutations and the clinicopathological features and EGFR-TKI efficiency.

METHODS

EGFR mutation was detected in 120 patients and KRAS mutation in 104 patients with NSCLC in Peking Union Medical College Hospital from March 2009 to December 2010, and the correlation of the gene mutations with the clinicopathological features and EGFR-TKI efficiency was analyzed in the study.

RESULTS

EGFR mutation was detected in 44 of 120 (36.7%) patients with NSCLC, in which three types of EGFR gene mutations were found: deletion in exon 19, exon 21 L858R (2573T > G) and Exon 21 L861Q (2582T > A) mutations. There were 29(24.2%) patients with EGFR exon 19 deletion, 14 (11.7%) patients with EGFR exon 21 L858R mutation and one (0.8%) with EGFR exon 21 L861Q mutation in the patients. All the mutations were single point mutations, and no multiple points mutations detected. EGFR mutation rate of bronchioloalveolar carcinoma and adenocarcinoma were higher than that of non-adenocarcinoma (P = 0.009). EGFR mutation rate was higher in female patients or patients without smoking history than male patients or patients with smoking history (P = 0.014, P = 0.001, respectively) in NSCLC patients. EGFR mutation rate was higher in patients without smoking history or patients with well-differentiated carcinoma than patients with smoking history or patients with moderately-and poorly-differentiated carcinoma (P = 0.008, P = 0.018, respectively). There was no difference in prognosis and EGFR-TKI treatment response rate between EGFR mutation patients and EGFR wild-type patients. Nine (8.7%) patients with KRAS mutation were detected in 104 NSCLC patients. There were four types of KRAS gene mutations detected: KRAS Gly12Ala (GGT > GCT), KRAS Gly12Arg (GGT > CGT), KRAS Gly12Val (GGT > GTT) and KRAS Gly12Cys (GGT > TGT). There were 4 patients with Cys mutation, 2 with Arg mutation, 2 with Val mutation and 1 with multiple points mutation of both Cys and Arg in exon 12. No relationship was found between KRAS mutation and clinicopathological feature either in NSCLC or in adenocarcinoma. Prognosis was worse in patients with KRAS mutation than in wild-type patients (P = 0.008). No patient with both EGFR and KRAS mutation was detected.

CONCLUSIONS

EGFR mutation rate is related with gender, smoking history and pathological type in NSCLC patients, and is also related with differentiation and smoking history in adenocarcinoma patients. And prognosis is worse in patients with KRAS mutation than that with wild type.

摘要

目的

研究中国非小细胞肺癌（NSCLC）患者表皮生长因子受体（EGFR）和 Kirsten 大鼠肉瘤病毒癌基因（KRAS）的基因突变情况，并分析基因突变与临床病理特征及 EGFR 酪氨酸激酶抑制剂（EGFR-TKI）疗效的关系。

方法

2009 年 3 月至 2010 年 12 月，在北京协和医院对 120 例 NSCLC 患者检测 EGFR 突变，对 104 例 NSCLC 患者检测 KRAS 突变，并分析基因突变与临床病理特征及 EGFR-TKI 疗效的相关性。

结果

120 例 NSCLC 患者中，44 例（36.7%）检测到 EGFR 突变，共发现 3 种类型的 EGFR 基因突变：外显子 19 缺失、外显子 21 L858R（2573T＞G）和外显子 21 L861Q（2582T＞A）突变。其中，外显子 19 缺失 29 例（24.2%），外显子 21 L858R 突变 14 例（11.7%），外显子 21 L861Q 突变 1 例（0.8%）。所有突变均为单点突变，未检测到多点突变。细支气管肺泡癌和腺癌的 EGFR 突变率高于非腺癌（P = 0.009）。NSCLC 患者中，女性患者或无吸烟史患者的 EGFR 突变率高于男性患者或有吸烟史患者（分别为 P = 0.014，P = 0.001）。无吸烟史患者或高分化癌患者的 EGFR 突变率高于有吸烟史患者或中低分化癌患者（分别为 P = 0.008，P = 0.018）。EGFR 突变患者与 EGFR 野生型患者的预后及 EGFR-TKI 治疗有效率无差异。104 例 NSCLC 患者中，9 例（8.7%）检测到 KRAS 突变。共检测到 4 种类型的 KRAS 基因突变：KRAS Gly12Ala（GGT＞GCT）、KRAS Gly12Arg（GGT＞CGT）、KRAS Gly12Val（GGT＞GTT）和 KRAS Gly12Cys（GGT＞TGT）。外显子 12 中有 4 例 Cys 突变、2 例 Arg 突变、2 例 Val 突变和 1 例 Cys 和 Arg 多点突变。在 NSCLC 及腺癌中，均未发现 KRAS 突变与临床病理特征有关。KRAS 突变患者的预后较野生型患者差（P = 0.008）。未检测到同时存在 EGFR 和 KRAS 突变的患者。