Elsevier

Clinical Oncology

Volume 27, Issue 1, January 2015, Pages 30-39
Clinical Oncology

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

https://doi.org/10.1016/j.clon.2014.09.014Get rights and content

Abstract

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.

Section snippets

Statement of Search Strategy and Sources of Information

We searched the PubMed, EMBASE, as well as Cochrane Library databases to identify the articles with the combination of the following key words: ‘epidermal growth factor receptor mutation’ or ‘EGFR mutation’ or ‘EGFR amplification’ or ‘EGFR expression’ or ‘KRAS mutation’, ‘lung’ or ‘pulmonary’ or ‘non-small cell lung cancer’ or ‘NSCLC’. Reference lists of original articles and review articles were also examined. The published language was limited to English and the literature search was

Search Strategy and Selection Criteria

We searched the PubMed, EMBASE, as well as Cochrane Library databases, to identify the articles with the combination of the following keywords: ‘epidermal growth factor receptor mutation’ or ‘EGFR mutation’ or ‘EGFR amplification’ or ‘EGFR expression’ or ‘KRAS mutation’, ‘lung’ or ‘pulmonary’ or ‘non-small cell lung cancer’ or ‘NSCLC’. Reference lists of original articles and review articles were also examined. The published language was limited to English and the literature search was

Literature Search and Study Characteristics

Figure 1 shows the selection steps. In total, 21 studies were meta-analysed in our study. Among these 21 studies, 13 were on EGFR mutations [14], [15], [16], [17], [18], [19], [20], [21], [22], [25], [31], [32], [33]; four on EGFR amplification [23], [24], [25], [26]; six on EGFR protein expression [15], [23], [27], [28], [29], [30]; 10 on KRAS mutations [15], [17], [19], [20], [21], [26], [27], [32], [34]. The number of patients in previously cited reports is shown in Table 1, Table 2. In our

Discussion

NSCLC is a major global health burden. Up to half of patients with NSCLC develop metastases at the time of the initial diagnosis, and more patients eventually experience metastases in the course of their disease [19]. At present, no final conclusion has yet been reached on the two theories for the metastatic process – that the metastatic potential was acquired in the early or advanced stage [11], [12]. Few studies evaluated the difference between primary tumours and subsequent metastases. Even

Conclusions

Our study failed to find a significant difference in overall EGFR mutation rate, gene amplification, protein expression and overall KRAS mutation rate between primary and metastatic NSCLC. By further analysis of inconsistent EGFR or KRAS mutation types, we found there was no significant difference between loss of mutation rate and the occurrence of mutation rate. These findings may have significant implications in the clinical management of NSCLC patients.

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