Meta-analysis of Epidermal Growth Factor Receptor and KRAS Gene Status between Primary and Corresponding Metastatic Tumours of Non-small Cell Lung Cancer

The epidermal growth factor receptor (EGFR) and KRAS gene status in paired primary non-small cell lung cancer (NSCLC) and metastatic tumours has been investigated by many studies, but remains controversial. We systematically reviewed studies in English of EGFR and KRAS gene status in primary and corresponding metastatic NSCLC up to 15 January 2014. Studies were selected rigorously from PubMed, EMBASE, as well as Cochrane Library databases. We carried out a meta-analysis to clarify EGFR mutations, EGFR amplification, positive rate of EGFR protein expression and KRAS mutations in primary and corresponding metastatic NSCLC. Our data suggested that the overall EGFR mutation rate, gene copy number, protein expression were not different between primary tumours and corresponding metastases, with the pooled odd ratios and 95% confidence interval 1.043 (0.686-1.586, P = 0.844), 0.604 (0.355-1.027, P = 0.063) and 1.447 (0.948-2.208, P = 0.087), respectively. The overall KRAS mutation rate of primary tumours was not different from that of matched metastases, with the odds ratio and 95% confidence interval being 1.224 (0.808-1.856, P = 0.340). The discordant rates of EGFR and KRAS mutations in paired primary and metastatic NSCLC were 14.5 and 16.7%, respectively. Among the discordant gene mutations in primary and metastatic lesions, the frequency of occurrence of mutation was not different from the frequency of loss of mutation for EGFR (P = 0.093) and KRAS gene (P = 0.227). These results indicate that EGFR and KRAS mutations are present frequently in metastases and occur before metastasis. Therefore, routine analysis of EGFR or KRAS gene status both in primary and metastatic tumours is not recommended.