Comparison of Epidermal Growth Factor Receptor Mutations between Primary Tumors and Lymph Nodes in Non-small Cell Lung Cancer: a Review and Meta-analysis of Published Data

Abstract

Background: Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) can predict the clinical response to tyrosine kinase inhibitor (TKI) therapy. However, EGFR mutations may be different in primary tumors (PT) and metastatic lymph nodes (MLN). The aim of this study was to compare EGFR mutations between PT and the corresponding MLN in NSCLC patients, and provide some guidelines for clinical treatment using TKI therapy. Materials and Methods: A systematic review and meta-analysis was performed with several research databases. Relative risk (RR) with the 95% confidence interval (CI) were used to investigate the EGFR mutation status between PT and the corresponding MLN. A random-effects model was used. Results: 9 publications involving 707 patients were included in the analysis. It was found that activation of EGFR mutations identified in PT and the corresponding MLN was 26.4% (187/707) and 19.9% (141/707), respectively. The overall discordance rate in our meta-analysis was 12.2% (86/707). The relative risk (RR) for EGFR mutation in PT relative to MLN was 1.33 (95%CI: 1.10-1.60; random-effects model). There was no significant heterogeneity between the studies (I 2 =5%, p=0.003). Conclusions: There exists a considerable degree of EGFR mutation discrepancy in NSCLC between PT and corresponding MLN, suggesting that tumor heterogeneity might arise at the molecular level during the process of metastasis.

Characterization of genetic alterations in brain metastases from non‐small cell lung cancer

“…. The majority of previous studies demonstrated that the overall concordance rate of EGFR mutation status was about 87.8% between primary tumor and paired metastatic lymph nodes . A higher concordance rate was observed in Sun et al .…”

Mutation status concordance between primary lesions and metastatic sites of advanced non-small-cell lung cancer and the impact of mutation testing methodologies: a literature review

“…However, depending on patient ability and/or willingness to undergo sampling, whether samples are available or evaluable, and differing diagnostic practices between countries [ 12 , 13 , 21 – 25 ], either the primary tumour or a metastatic lesion may be biopsied [ 26 ]. However, the concordance in mutation status between matched primary and metastatic tumours is the subject of debate [ 3 , 27 – 33 ], with limited understanding as to whether discordance reflects actual heterogeneity in mutations, or is an artifact of technical/sensitivity limitations in testing methodology [ 34 – 43 ]. Nevertheless, given that the collection of multiple invasive samples from a patient with NSCLC is undesirable, it is important to ascertain whether the mutation status of an individual patient’s NSCLC can be accurately characterised from biopsies of either the primary or metastatic sites.…”

Usefulness of conventional transbronchial needle aspiration in the diagnosis, staging and molecular characterization of pulmonary neoplasias by thin-prep based cytology: experience of a single oncological institute

“…At the moment predictive molecular tests are usually performed on the primary tumor (T). Although the first studies correlating genetic alterations in metastatic lymph nodes have been deluding (36)(37)(38), other reports demonstrated that primary tumor mutational status not always correlate with the metastatic lymph node genetic status (39). Chen et al showed that the therapeutic response to tyrosine kinase inhibitor (TKI) acting on EGFR is more pronounced in patients with mutated tumor in the metastatic foci (40): therefore the mutational status of the N component could be more predictive of therapy response than that of the primary tumor (41).…”