Mutational status of the epidermal growth factor receptor (EGFR) gene in thymomas and thymic carcinomas.

Epithelial tumours of the thymus (thymoma, thymic carcinoma) are rare tumours of the anterior mediastinum. Current treatment options of advanced stage thymomas and thymic carcinomas include a multimodal therapy with radio- and chemotherapy as well as surgery. In recent years, new therapeutic targets such as EGFR (epidermal growth factor receptor), COX-2 and KIT have emerged as new potential therapeutic targets. So far, EGFR mutational status of different subtypes of epithelial tumours of the thymus has been analyzed only inappropriately. We have investigated 20 different subtypes of thymomas (type A, AB, and B3) and thymic carcinomas for mutations in exons 18, 19, 20, and 21 of the EGFR gene and performed immunohistochemistry for EGFR. Concerning immunohistochemistry, most of the cases (17/20) had a strong positive staining. Although sequence alterations were found in four samples, none of these alterations led to amino acid changes in the tyrosine kinase domain of EGFR comparable to those in non-small cell lung cancer. Thus EGFR-expression in thymic tumours does not rely on mutations in critical functional (activation) domains of the EGFR-gene. Experimental and therapeutic approaches have to consider this difference.