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Updated: Jun 5, 2026
Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
Immunohistochemical and molecular analysis of tyrosine kinase activity in desmoid tumors
Nancy L Cho1, Adelaide M Carothers, Hira Rizvi
1Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA. mbertagnolli@partners.org
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 β-catenin in five of six (83%) DT relative to matched normal tissue by immunoblot analysis. By immunohistochemistry, β-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, β-catenin tyrosine phosphorylation (p-Y) among tumors was variably increased, despite the increased amount of total β-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.
Insights
Desmoid tumors (DT) show increased beta-catenin, but tyrosine kinase c-Src and c-Kit activity varies. This suggests tyrosine kinase inhibitors (TKI) may treat DT through mechanisms other than targeting these specific kinases.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Optimal treatment for desmoid tumors (DT) remains undefined.
- Partial responses to tyrosine kinase inhibitors (TKI) have been observed.
- The roles of c-Src and c-Kit in desmoid tumorigenesis require further investigation.
Purpose of the Study:
- To investigate the expression and activity of beta-catenin, c-Src, and c-Kit in desmoid tumors.
- To understand the potential mechanisms of TKI response in desmoid tumors.
Main Methods:
- Collected six desmoid tumor (DT) and matched normal tissue samples.
- Utilized immunohistochemistry, immunoblot analysis, and immunoprecipitation to analyze protein levels and activity.
- Examined beta-catenin, c-Src, and c-Kit expression and phosphorylation.
Main Results:
- Increased beta-catenin levels and nuclear localization were observed in 83% of DT samples.
- Variable expression of total and activated c-Src and c-Kit was found in DT.
- Beta-catenin tyrosine phosphorylation varied among tumors despite increased total beta-catenin.
Conclusions:
- c-Src and c-Kit activity in DT is heterogeneous, reflecting the disease's nature.
- Clinical response to TKI in DT may involve mechanisms independent of c-Src or c-Kit.
- Further research into DT biology is crucial for developing novel therapeutic strategies.
