[Therapy-relevant mutations of receptor tyrosine kinases in malignant thymomas and thymic carcinomas: a therapeutic perspective].
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.
Ströbel
P
P
Institut für Pathologie, Universitätsklinikum Mannheim der Universität Heidelberg.
Knop
S
S
Einsele
H
H
Müller-Hermelink
H K
HK
Marx
A
A
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000068818:Cetuximab; D066246:ErbB Receptors / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013945:Thymoma / Q000235:genetics* / Q000473:pathology; D013953:Thymus Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D000068818:Cetuximab