title: Immunohistochemical and molecular analysis of tyrosine kinase activity in desmoid tumors.
abstract: 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.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA. mbertagnolli@partners.org
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Cho
authors.forename: Adelaide M
authors.initials: AM
authors.lastname: Carothers
authors.forename: Hira
authors.initials: H
authors.lastname: Rizvi
authors.forename: Rian M
authors.initials: RM
authors.lastname: Hasson
authors.forename: Mark
authors.initials: M
authors.lastname: Redston
authors.forename: Monica M
authors.initials: MM
authors.lastname: Bertagnolli
mesh_terms: D000328:Adult; D000081247:CSK Tyrosine-Protein Kinase; D002471:Cell Transformation, Neoplastic; D005260:Female; D018222:Desmoid Tumors / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*; D019061:src-Family Kinases
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human