Immunohistochemical and Molecular Analysis of Tyrosine Kinase Activity in Desmoid Tumors

Background. Optimal surgical and medical therapy for the treatment of desmoid tumors (DT) is still undefined. Partial response to tyrosine kinase inhibitors (TKI) has previously been described. Here, we examined the role of the tyrosine kinases c-Src and c-Kit in driving desmoid tumorigenesis. Methods. Six consecutive DT and matched normal tissues were collected from the operating room. Tissues were embedded in paraffin for immunohistochemical analysis, and protein lysates were prepared for immunoblot and immunoprecipitation. Results. We found increased levels of beta-catenin in five of six (83%) DT relative to matched normal tissue by immunblot analysis. By immunohistochemistry, beta-catenin expression was also increased in DT and localized to the nucleus. In contrast, we observed variable levels of total and activated c-Src and c-Kit expression in DT compared with normal tissue. Finally, beta-catenin tyrosine phosphorylation (p-Y) among tumors was variably increased, despite the increased amount of total beta-catenin in tumors. Conclusions. Our results suggest that c-Src and c-Kit activity in DT is variable, consistent with the heterogeneous nature of this disease. Clinical response to TKI in DT may be via alternative mechanisms unrelated to c-Src or c-Kit activity. Further insight into DT biology will help identify novel drug regimens to limit the morbidity and mortality associated with this disease. (C) 2012 Elsevier Inc. All rights reserved.