The epidermal growth factor receptor (EGFR) gene has recently been reported to be mutated in a subset of non-small cell lung cancers (NSCLC), with the mutations being correlated with the patients' drug sensitivity to gefitinib, an EGFR kinase inhibitor. In this study, we searched for EGFR mutations in patients with lung cancer using primary tumor specimens obtained at initial surgery and examined whether their recurrent tumors showed a response to gefitinib depending on the presence of the activating mutation. Among 12 lung cancers that were treated with gefitinib after recurrence, we found that all four tumors which showed a response to gefitinib had an activating mutation in EGFR, whereas none of the remaining eight tumors had a mutation. Southern blot analysis showed that two of the four responsive tumors had the EGFR gene amplification. We also examined another 73 NSCLC specimens (47 males and 26 females; 53 adenocarcinomas and 20 non-adenocarcinomas) which were not treated with gefitinib to determine whether NSCLCs with an EGFR mutation have different clinicopathological properties and/or unique genetic alterations of the other cancer-associated genes. We found that 13 (18%) of 73 tumors had a mutation of the EGFR gene, with the most being detected in female adenocarcinomas. Comparing the alterations in KRAS and P53 with the EGFR mutation, we found that 10 tumors with the KRAS mutation did not have an EGFR mutation, suggesting that each mutation occurs exclusively during the development of lung cancer. These results suggest that the mutation analysis of the EGFR gene using the specimens obtained at surgery might be useful in selecting the appropriate treatment(s) for recurrent lung cancer patients. © 2005 Elsevier Ireland Ltd. All rights reserved.
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