The High Proportion of Discordant EGFR Mutations among Multiple Lung Tumors

SIMPLE SUMMARY: Lung cancer is one of the leading causes of cancer-related mortality worldwide. The incidence of multiple primary lung cancers has been increasing. In addition to the identification of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, the evaluation of the EGFR mutation status in lung cancer is important to devise optimal treatment strategies. In this study, the EGFR mutation status in multiple primary lung cancers was examined, and its discordance rate in individual tumors was determined to be high. Our findings reveal the importance of EGFR mutation analysis in individual tumors of multiple primary lung cancers. ABSTRACT: The prevalence of multiple lung cancers has been increasing recently. Molecular analysis of epidermal growth factor receptor (EGFR) mutations in individual tumors of multiple lung cancers is essential for devising an optimal therapeutic strategy. The EGFR mutation status in multiple lung cancers was evaluated to determine its therapeutic implications. In total, 208 tumors from 101 patients who underwent surgery for multiple lung cancers were analyzed. Individual tumors were subjected to histological evaluation and EGFR analysis using a real-time polymerase chain reaction. Additionally, EGFR-wildtype tumors were subjected to next-generation sequencing (NGS). EGFR mutations were detected in 113 tumors from 72 patients, predominantly in females (p < 0.001) and non-smokers (p < 0.001). Among patients with at least one EGFR-mutant tumor, approximately 72% of patients (52/72) had different EGFR mutations in individual tumors. NGS analysis of EGFR-wildtype tumors from 12 patients revealed four and eight cases with concordant and discordant molecular alterations, respectively. These findings revealed a high proportion of discordant EGFR mutations among multiple lung tumors. Hence, EGFR analysis of individual tumors of multiple lung tumors is essential for the evaluation of clonality and the development of an optimal treatment strategy.