title: Mutations of epidermal growth factor receptor of non-small cell lung cancer were associated with sensitivity to gefitinib in recurrence after surgery.
abstract: 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.
authors.affiliation: Department of Clinical Preventive Medicine, Nagoya University School of Medicine, Nagoya 466-8560, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kondo
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fukui
authors.forename: Hiromu
authors.initials: H
authors.lastname: Yoshioka
authors.forename: Kohei
authors.initials: K
authors.lastname: Yokoi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Nagasaka
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Imaizumi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kume
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Kaoru
authors.initials: K
authors.lastname: Shimokata
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sekido
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000601:surgery; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics* / Q000601:surgery; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D005784:Gene Amplification; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000601:surgery; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012727:Sex Characteristics
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib