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Background: CD117 is a thyrosin kinase receptor encoded by c-kit proto-oncogene. It is expressed during normal development in some tissues and also in a subset of neoplasia especially gastrointestinal stromal tumors (GISTs). Treatment with thyrosin kinase inhibitors (e.g., Imatinib) is useful in CD117- positive GISTs. The goal of this study is to investigate the expression of CD117 in glial tumors as a potential diagnostic marker and target for therapy. Materials and Methods: in this descriptive-analytical study, paraffin- embedded tissue blocks from 50 cases of glial tumors (various histological types and grades) were selected in a convenience sampling for the CD117 immunhistochemical study including expression of the marker, staining intensity, and percentage of the stained cells. The results were analyzed by Chi-square and Mann-Whitney tests. Results: CD117 expression was detected in about 76% of glial tumors but the frequency of the expression showed no statistically significant relationship with the tumor type (P = 0.829). Although CD117 immunoreactivity was more frequent in high-grade tumors (84%) compared to the low-grade ones (68%), no statistically significant relationship was found between the CD117 expression and grade of the tumor (P = 0.09). Staining intensity and percentage of stained cells in high-grade tumors were significantly more than in low-grade tumors (P values of 0.046 and 0.023, respectively). Conclusion: according to the statistically significant difference in the staining intensity and percentage of the stained cells between the low-grade and high-grade glial tumors, these two parameters may be useful for making distinction between various grades of these tumors. Moreover, according to the prominent expression of CD117 in high-grade gliomas, these tumors may be potential candidates for treatment with thyrosin kinase inhibitors.