Expression of c-kit in Ewing family of tumors: a comparison of different immunohistochemical protocols.
Ewing sarcoma is a small round blue cell tumor with a high incidence of metastasis and poor survival. The tyrosine kinase receptor, c-kit, is a growth factor receptor that is expressed in a variety of tumors including Ewing sarcoma. Blockade of c-kit by imatinib mesylate (Gleevec; Novartis Pharmaceuticals Corp, East Hanover, NJ) has been successfully used in the treatment of chronic myelogenous leukemia and gastrointestinal tumors. Detection of c-kit expression in Ewing sarcoma indicates a possible role of c-kit in tumor progression and a potential use of anti-c-kit therapy in Ewing sarcoma. Ki-67 is a proliferation marker found at all stages of the cell cycle. Expression of c-kit and Ki-67 was studied in 17 patients with Ewing sarcoma. Sections from paraffin-embedded tumor samples were immunostained, using standard immunohistochemical protocols, with c-kit and Ki-67 monoclonal antibodies, polyclonal c-kit antibody without antigen retrieval, and c-kit polyclonal antibody with antigen retrieval. Eleven out of 17 cases (65%) stained with c-kit monoclonal antibody; the staining was diffuse in 6/17 (35%) cases. C-kit expression did not correlate with Ki-67 proliferation rates. Using the polyclonal c-kit-antibody without antigen retrieval methods, c-kit expression was demonstrated in 1/11 (9%) cases. Incorporating antigen retrieval methods, c-kit expression increased to 53%. Concordance between monoclonal antibodies in detecting c-kit expression was observed in 12/17 cases (71%). We conclude that c-kit is variably expressed in Ewing sarcoma, using either monoclonal or polyclonal antibodies. Detection of c-kit expression in Ewing sarcoma improves with the use of antigen retrieval methods.
Ahmed
Atif
A
Section of Pediatric Tumor Biology and Ultrastructural Pathology, National Cancer Institute, NIH Building 10, Rm 2A10, 10 Center Drive, 20892, Bethesda, MD, USA. ahmeda@mail.nih.gov
Gilbert-Barness
Enid
E
Lacson
Atilano
A
D000293:Adolescent; D000328:Adult; D000906:Antibodies; D014408:Biomarkers, Tumor; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D012189:Retrospective Studies; D012512:Sarcoma, Ewing / Q000378:metabolism* / Q000473:pathology
D000906:Antibodies; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019009:Proto-Oncogene Proteins c-kit