OverviewMeta-analysis of Epidermal Growth Factor Receptor and KRAS Gene Status between Primary and Corresponding Metastatic Tumours of Non-small Cell Lung Cancer
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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Cited by (26)
On target: Rational approaches to KRAS inhibition for treatment of non-small cell lung carcinoma
2021, Lung CancerCitation Excerpt :In an analysis of KRAS-mutant tumors in NSCLC, some samples from individual tumors had wild-type KRAS, while other tumors had two different KRAS mutations [50]. Other studies in NSCLC have reported limited heterogeneity in KRAS mutational status within and between tumors [51,52], illustrating the complexity of KRAS genetics. The heterogeneity in KRAS mutational status observed in NSCLC is also seen in other solid tumors: in metastatic colorectal cancer (CRC), in which ~40% of patients have a KRAS mutation [18], ~10% of patients had discordant KRAS mutational status within primary tumors [53] or between a primary tumor and metastases [54].
Comparison of genetic profiles among primary lung tumor, metastatic lymph nodes and circulating tumor DNA in treatment-naïve advanced non-squamous non-small cell lung cancer patients
2018, Lung CancerCitation Excerpt :This can partially explain the lack of difference in PFS between patients with and without discordance. Some studies have demonstrated a high concordance between primary tumor and metastatic lymph node in NSCLC [30,31]. The main reason for discordance was sequencing method, direct sequencing was used in most of these studies with high discordance rate [32,33].
Discrepancy in BRAF status among patients with metastatic malignant melanoma: A meta-analysis
2017, European Journal of CancerThe Current and Evolving Role of PET in Personalized Management of Lung Cancer
2016, PET ClinicsCitation Excerpt :EGFR and KRAS gene status in paired NSCLC and metastatic tumors had been investigated by many studies, but remained controversial. Wang and Wang48 performed a metaanalysis to determine the role of EGFR and KRAS mutations in primary and corresponding metastatic tumors of NSCLC. The discordant rates of EGFR and KRAS mutations in paired primary and metastatic NSCLC were found to be 14.5% and 16.7%, respectively.
Detecting Tumor Metastases: The Road to Therapy Starts Here
2016, Advances in Cancer ResearchCitation Excerpt :In another study, Westood and colleagues analyzed 12 databases and verified EGFR mutation status in NSCLCs (Westwood et al., 2014). Consistent with Wang and Wang's (2015) observation they also did not find any greater accuracy for EGFR mutation as a diagnostic measure. However, some positive correlations of EGFR with breast cancer metastasis are evident.