50-70% of patients with malignant thymic epithelial tumors (thymomas or thymic carcinomas) cannot be cured by current treatment strategies and are therefore candidates for second line therapies. METHODS: Malignant thymomas and thymic squamous cell carcinomas (TSCC) were analyzed by genomic sequencing and functional tests using ex vivo explant cell cultures to study alterations of the receptor tyrosine kinases c-Kit and epidermal growth factor receptor (EGFR) and their relevance for tumor cell function. RESULTS: Overexpression of c-Kit was observed only in TSCC, but not in thymomas. In spite of overexpression in almost 90% of TSCC, c-Kit mutations were very infrequent (10%). A strong expression of the EGFR was observed in 70% of thymomas and 35% of TSCC. Mutations of exons encoding extra- or intracellular domains were not observed in a single case (n=40). However, in vitro studies with epithelial explant cell cultures of these tumors suggested that treatment with Cetuximab was effective in a subset of cases, while others were resistant. CONCLUSIONS: Our findings may forecast therapeutic responses to emerging target treatments in malignant thymomas and thymic carcinomas and may help to develop novel strategies.
