Imatinib mesylate (Gleevec)-targeted kinases are expressed in uterine sarcomas

The purpose of this study was to determine whether 3 tyrosine kinases known to be inhibited by imatinib mesylate are expressed in a variety of uterine sarcomas. The authors assessed c-kit, ab1, and platelet-derived growth factor receptor-beta (PDGFR-beta) expression in 8 endometrial stromal sarcomas (ESSs), 5 leiomyosarcomas (LMSs), 4 high-grade endometrial sarcomas (HGESs), and 21 malignant mixed mullerian tumors (MMMTs). Tissue sections were stained with commercially available antibodies for e-kit, ab1, and PDGFR-beta. Staining intensity was described as 0 (no staining), +1 (weak), +2 (moderate), and +3 (strong). Positive staining was defined as moderate to strong if found in more than 10% of tumor cells. Expression of e-kit ranged from 0% in LMSs to 25% in HGESs. Protein expression of ab1 was more significant, ranging from 25% in LMSs and ESSs to 43% in MMMTs. Only 1 LMS sample stained focally for ab1 (+1). AN expression was observed in only the carcinomatous elements of the MMMTs, with diffuse staining in the cytoplasm and nucleus. In most, the staining intensity was +2. All tumors stained positive for PDGFR-beta. MMMT samples showed PDGFR-beta expression in both the carcinomatous and sarcomatous portions. In all samples, staining for PDGFR-beta was concentrated at the cell membrane and diffusely in the cytoplasm. These results indicate that many uterine sarcomas express I or more of the kinases targeted by imatinib mesylate and that further investigation of imatinib as a therapy for uterine sarcomas is warranted.