Epidermal growth factor receptor mutations in lung cancers.

In 2004, two groups reported somatic mutations in the gene for the epidermal growth factor receptor (EGFR) in patients with non-small cell lung cancer (NSCLC), which were highly correlated with the clinical response to the anticancer drug, gefitinib. Since then, a tremendous amount of knowledge has accumulated, and sheds light on significant oncological properties as well as the clinical relevance of this mutation, which could be applicable to other malignancies. The EGFR mutations are distributed throughout the kinase domain, but a deletion in exon 19 and the point mutation L858R in exon 21 account for approximately 90%, which confer a greater response to gefitinib treatment, compared with other types of EGFR mutations. These EGFR mutations in the tyrosine kinase domain are seldom acquired in cancers of the other organs and the mutations preferentially involve a subset of lung cancers, which are clinicopathologically characterized by female sex, non-smoking, adenocarcinoma histology and East Asian ethnicity. In Japan, the EGFR mutations are detected in approximately 30% of overall NSCLC and approximately 40% of surgically resected adenocarcinomas. The morphological features of adenocarcinomas harboring the mutations were reported to be frequent in those with bronchioloalveolar features, but it is suggested that the cellular lineage of the putative original cells of the cancers refines the subset more clearly. In the present study the current knowledge of EGFR mutations is reviewed, insights from which raise many further questions, and thus suggest new directions for future research.