Lung adenocarcinoma harboring mutations in the ERBB2 kinase domain

Mutations in the ERBB2 kinase domain have been reported in non-small cell lung cancer (NSCLC). Here, we describe a detailed search for ERBB2 gene mutations in tumors derived from NSCLC patients. Tumor specimens from 223 patients who underwent resection for NSCLC were examined for the presence of mutations in exons 19 and 20 of the ERBB2 gene. Correlations were then made between the expression of these mutations and the clinical characteristics of the patients from which they were derived as well as the tumor's pathological features. ERBB2 mutations were observed in four of the above tumors (1.8%), all of which were adenocarcinomas. All ERBB2 mutations were in-frame insertions that occurred in exon 20. The patients from whom these tumors were derived were nonsmokers. Three of the tumors were of the papillary subtype, and one was a mixed subtype that consisted of acinar, papillary, and solid components. None of the tumors had a bronchio-alveolar component nor did they have epidermal growth factor receptor or K-ras codon 12 mutations. In conclusion, patients with these tumors tended to be nonsmokers who had clinical features similar to those of lung cancer patients whose tumors expressed epidermal growth factor receptor mutations, although their tumors showed slightly different pathological features.