Verhandlungen der Deutschen Gesellschaft fur Pathologie · 2007
[Therapy-relevant mutations of receptor tyrosine kinases in malignant thymomas and thymic carcinomas: a therapeutic perspective].
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Ströbel P, Knop S, Einsele H, Müller-Hermelink H K, Marx A
Аннотация
UNLABELLED: 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.
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.