YHS and XPH performed the experiments and were involed in drafting the article. All authors have read and approved the final manuscript.”
“Introduction Lung cancer is one of the leading causes of cancer-related mortality both in China and throughout the world [1, 2]. Non-small cell lung cancer (NSCLC) accounts for75-80% of all lung cancer . Standard therapeutic strategies such as surgery, chemotherapy, or radiotherapy have
reached a plateau . Significant advances in the research of the biology and molecular mechanisms of cancer have allowed the development of new molecularly targeted agents for the treatment of NSCLC [4–8]. One such target is the epidermal growth factor receptor Selumetinib mw (EGFR), a 170-kDa trans-membrane glycoprotein and member of erbB family. Small molecule tyrosine kinase inhibitors (TKI), such as gefitinib and erlotinib, disrupt EGFR kinase activity by binding the adenosine triphosphate pocket within the catalytic region of the tyrosine kinase domain . Currently, both
gefitinib and erlotinib are used for treatment of patients with advanced NSCLC. TKI clinical trials have shown that these agents have dramatic effect on the subset of NSCLC patients with somatic mutations in the tyrosine kinase domain of the EGFR gene, whereas the presence of KRAS mutations seems to be correlated with primary resistance to these agents [10–15]. So it is necessary to identify the mutation status of KRAS and EGFR for selection Cilomilast of patients who are more likely to benefit from TKI. Although almost 70% of patients with NSCLC present with locally advanced or metastatic disease at the
time of diagnosis [16, 17], KRAS and EGFR mutation status is most commonly assessed only in the primary tumor tissue based on the assumption that primary and metastases are pathologically concordant. from However, 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 [18–20]. It is still unclear whether KRAS and EGFR mutation status in primary tumors is reflected in their corresponding metastases in Chinese patients with NSCLC, although several recent relevant studies in western countries have been performed and published [21–26]. In the present study, we investigate KRAS and EGFR mutation status using PCR-based sequencing analyses in 80 primary tumor samples and their corresponding local lymph node metastases from Chinese patients with NSCLC. The goal is to determine whether KRAS and EGFR mutation profile is stable during the metastatic progress and to investigate the clinical usefulness of mutational analyses in primary tumor versus in metastases for planning EGFR-targeted therapies for the treatment of patients with NSCLC.