Abstract

BackgroundEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) have been widely used for the treatment of non-small cell lung cancer (NSCLC). KRAS and EGFR somatic mutations in NSCLC may predict resistance and responsiveness to TKI, respectively. Nevertheless, most research to date has been conducted on samples from primary tumors. For many patients with advanced disease, their samples can only be obtained from metastases for test. The molecular characteristics of metastasized tumors may be different from those of primary tumors.Materials and methodsMutation status of KRAS and EGFR between primary tumors and local lymph node metastases of 80 Chinese patients with NSCLC were analyzed by direct sequencing. Five of them were given gefitinib as neoadjunvant treatment after the EGFR-TKI sensitive mutations were detected in their biopsies of mediastinal lymph nodes metastases. McNemar's test was used to compare the EGFR and KRAS mutation status between primary tumors and corresponding local lymph node metastases. Data evaluation was carried out with SPSS_13.0 statistical software.ResultsAmong the 160 samples, one primary tumor and seven metastases were identified with KRAS mutations and 21 primary tumors and 26 metastases were found to have EGFR mutations. KRAS and EGFR mutation status was different between primary tumors and corresponding metastases in 6 (7.5%) and 7 (8.75%) patients, respectively. One patient with no TKI sensitive mutations detected in the primary tumor showed disease progression.ConclusionOur results suggest that a considerable proportion of NSCLC in Chinese population showed discrepancy in KRAS and EGFR mutation status between primary tumors and corresponding metastases. This observation may have important implication for the use of targeted TKI therapy in the treatment of NSCLC patients.

Highlights

  • Lung cancer is one of the leading causes of cancerrelated mortality both in China and throughout the world [1,2]

  • Among the 160 samples, one primary tumor and seven metastases were identified with KRAS mutations and 21 primary tumors and 26 metastases were found to have epidermal growth factor receptor (EGFR) mutations

  • KRAS and EGFR mutation status was different between primary tumors and corresponding metastases in 6 (7.5%) and 7 (8.75%) patients, respectively

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Summary

Introduction

Lung cancer is one of the leading causes of cancerrelated mortality both in China and throughout the world [1,2]. Non-small cell lung cancer (NSCLC) accounts for75-80% of all lung cancer [3] Standard therapeutic strategies such as surgery, chemotherapy, or region of the tyrosine kinase domain [9]. It has been known that lung cancers are often heterogeneous at the molecular level even within the same tumor and many key molecular alterations may occur during metastatic progression [18,19,20] It is still unclear whether KRAS and EGFR mutation status in primary tumors is reflected in their corresponding metastases in Chinese patients with NSCLC, several recent relevant studies in western countries have been performed and published [21,22,23,24,25,26]. The molecular characteristics of metastasized tumors may be different from those of primary tumors

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