Background and objective: Epidermal growth factor receptor (EGFR) and KRAS status were particularly critical for the choice of first-line targeted therapy of non-small cell lung cancer (NSCLC), while the primary tumor and metastases might be different in the EGFR and KRAS gene status. The aim of this pooled analysis is to compare EGFR and KRAS status in matching primary NSCLC and metastases and further to guide clinical practice.
Methods: Systematic computerized searches of the Pubmed and Medline databases (up to May 10, 2010) meeting specified search criteria were performed, followed by a further screening according to inclusive and exclusive criteria.
Results: Fourteen articles were selected into the final meta-analysis with paired primary and metastatic cases of 598. Expression level of EGFR protein and mutation frequency of KRAS gene in primary tumors were higher than that in metastases, relative risk (RR)=1.13 (95%CI: 0.98-1.31, P=0.09) and RR=1.39 (95%CI: 0.95-2.03, P=0.09), respectively. EGFR gene copy number in metastases was higher than that in primary tumor, RR=0.74 (95%CI: 0.53-1.02, P=0.06). There was no statistically significant difference of EGFR mutation frequency in primary tumors and metastases (P=0.31). The discordant rate in primary and metastases was 17.09% for EGFR mutation, 27.07% for EGFR amplification, 27.84% for EGFR protein expression and 25.91% for KRAS mutation.
Conclusions: The systematic analysis showed that the EGFR mutation status in primary lung cancer and corresponding metastases was more stable than KRAS gene. KRAS mutation in primary lung cancerous foci seems to better reflect systemically cancerous genetic characteristics of KRAS gene. Determination of KRAS gene status based merely on metastatic foci might lead to more resistant selections of EGFR tyrosine kinase inhibitor (TKI) therapy. Combined detection of EGFR and KRAS mutation from primary NSCLC foci might serve as a better predictive biomarker for anti-EGFR targeted therapy.
背景与目的: 非小细胞肺癌EGFR和KRAS基因状态对肺癌一线靶向治疗的选择尤为关键，而原发肿瘤和转移瘤之间可能存在不同的EGFR和KRAS基因状态。本研究旨在系统评价比较配对的原发肺癌灶和转移灶EGFR和KRAS基因状态以指导临床实践。
方法: 通过Pubmed数据库检索所有符合检索条件的文献，末次检索日期2010年5月10日，根据纳入和排除标准进一步筛选。采用meta分析方法比对肺癌原发灶和转移灶中EGFR基因突变、扩增、EGFR蛋白表达和KRAS基因突变状态之间的差异。
结果: 14篇文献纳入meta分析，具有配对的原发灶和转移灶，598例 vs 598例。原发灶中EGFR蛋白表达和KRAS基因的突变频率高于转移灶，RR分别为1.13(95%CI: 0.98-1.31, P=0.09)和1.39(95%CI: 0.95-2.03, P=0.09)。转移灶中EGFR的基因拷贝数高于原发灶，RR=0.74(95%CI: 0.53-1.02, P=0.06)。EGFR基因在原发灶和转移灶中的突变频率无统计学差异(P=0.31)。原发灶和转移灶基因状态不一致率分别为：EGFR突变率为17.09%；EGFR扩增率为27.07%；EGFR蛋白表达率为27.84%；KRAS突变率为25.91%。
结论: 肺癌原发灶和相应转移灶中EGFR基因突变较KRAS基因状态更为稳定，原发灶中KRAS基因突变更能反映肺癌周身癌灶KRAS基因特征，单独对转移灶做KRAS状态分析可能会引入更多抵抗EGFR酪氨酸激酶抑制剂治疗的患者。联合检测原发灶中EGFR和KRAS基因突变可作为肺癌靶向治疗的疗效预测指标。