Abstract
9642 Background: c-kit functions as a tyrosine kinase receptor which becomes activated upon binding of its ligand SCF (stem-cell factor). Imatinib (Gleevec) is a small molecule known to inhibit the c-kit proto-oncogene, BCR-ABL tyrosine kinase and platelet-derived growth factor (PDGF) receptor. Imatinib has gained therapeutic relevance in the treatment of Chronic Myeloid Leukemia and has shown remarkable efficacy in the treatment of gastrointestinal stromal tumors (GIST). Because functions of Imatinib rely on the presence of mutated and activated c-kit, we studied the expression pattern for c-kit in a panel of different primary solid tumor sample. Methods: Paraffin-embedded tumor tissues from 295 patients were analyzed, including 51 breast cancer samples, 49 colorectal cancer, 21 renal cell carcinoma, 19 ovarian cancer, 18 sarcoma and 137 others. On these tumor samples c-kit expression was immunohistochemically evaluated using a polyclonal rabbit anti-human c-kit antibody (DAKO®). Staining results for each sample were scored from 0 (negative), + (weak), ++ (medium), +++ (strong). Results: c-kit immunopositivity was found in 37/295 (13%) cases, whereas 258/295 (87%) cases were negative. A strong expression of c-kit was found in 1 sarcoma, 1 GIST (gastrointestinal stromal tumor), 1 seminoma and 1 carcinoid. Of all 37 cases positive for c-kit, a strong expression was found in 4/37 (11%), c-kit medium expression in 11/37 (30%) and c-kit low reactivity was found in 22/37 (59%). Conclusions: Expression of c-kit was found in tumor samples with varying intensities. Out of 295 samples tested, 4 tumor samples (namely GIST, sarcoma, seminoma and carcinoid) showed high expression of c-kit. Analysis of the immunohistological results for c-kit expression lead to the definition of a scoring system in our hands: negative to strong c-kit expressing tumor samples. Further validation and correlation with clinical outcomes should lead to the definition of the relevance of this immunohistological classification. In addition, molecular analysis of c-kit mutations and activation status of the receptor should further help to predict the therapeutic implication of Imatinib in tumor patients. No significant financial relationships to disclose.
Published Version
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