Background: Overexpression of KIT, a tyrosine kinase receptor protein encoded by the protooncogene c-kit, is observed in human neoplasms such as gastrointestinal stromal. tumors (GISTs), myetoproliferative disorders, melanoma and seminoma. In patients with GIST, overexpression of mutated KIT within the tumor is predictive of response to molecular targeted therapy using imatinib. However, the rote of KIT expression in thymic carcinoma is not fully understood.
Methods: Thymic epithelial. tumors from 37 patients (17 thymic carcinomas and 20 thymomas) were examined. Immunohistochemical staining with anti-KIT polyclonal antibody and anti-CD5 was performed. Mutation analyses in the juxtamembrane domains, exons 9 and 11, and in the tyrosine kinase domains, exons 13 and 17, were undertaken using polymerase chain reaction (PCR) and direct DNA sequencing in KIT-positive samples.
Results: KIT- and CD5-positive staining was observed only in thymic carcinoma. Percentage of positive staining was 100% in squamous cell carcinoma, with no positive staining in other histologies, including atypical carcinoid. Mutation analysis of the KIT gene was performed in 11 squamous cell carcinomas, 1 adenocarcinoma and 1 adenosquamous ceit carcinoma. None of the tested samples showed mutations in any of the four exons.
Conclusions: Squamous cell carcinoma of the thymus frequently expressed KIT and CD5 proteins, whereas other tumors did not. Unlike GIST, overexpression of KIT does not necessarily indicate gene mutation in thymic carcinoma. KIT and CD5 appear useful for evaluating and subtyping thymic epithelial, tumors. (C) 2008 Elsevier Ireland Ltd. All rights reserved.