TY - JOUR
T1 - Imatinib mesylate (gleevec)-targeted kinases are expressed in uterine sarcomas
AU - Caudell, Jimmy J.
AU - Deavers, Michael T.
AU - Slomovitz, Brian M.
AU - Lu, Karen H.
AU - Broaddus, Russell R.
AU - Gershenson, David M.
AU - Ramondetta, Lois M.
PY - 2005/6/1
Y1 - 2005/6/1
N2 - 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, abl, and platelet-derived growth factor receptor-β (PDGFR-β) expression in 8 endometrial stromal sarcomas (ESSs), 5 leiomyosarcomas (LMSs), 4 high-grade endometrial sarcomas (HGESs), and 21 malignant mixed müllerian tumors (MMMTs). Tissue sections were stained with commercially available antibodies for c-kit, abl, and PDGFR-β. 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 c-kit ranged from 0% in LMSs to 25% in HGESs. Protein expression of abl was more significant, ranging from 25% in LMSs and ESSs to 43% in MMMTs. Only 1 LMS sample stained focally for abl (+1). Abl 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-β. MMMT samples showed PDGFR-β expression in both the carcinomatous and sarcomatous portions. In all samples, staining for PDGFR-β was concentrated at the cell membrane and diffusely in the cytoplasm. These results indicate that many uterine sarcomas express 1 or more of the kinases targeted by imatinib mesylate and that further investigation of imatinib as a therapy for uterine sarcomas is warranted.
AB - 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, abl, and platelet-derived growth factor receptor-β (PDGFR-β) expression in 8 endometrial stromal sarcomas (ESSs), 5 leiomyosarcomas (LMSs), 4 high-grade endometrial sarcomas (HGESs), and 21 malignant mixed müllerian tumors (MMMTs). Tissue sections were stained with commercially available antibodies for c-kit, abl, and PDGFR-β. 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 c-kit ranged from 0% in LMSs to 25% in HGESs. Protein expression of abl was more significant, ranging from 25% in LMSs and ESSs to 43% in MMMTs. Only 1 LMS sample stained focally for abl (+1). Abl 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-β. MMMT samples showed PDGFR-β expression in both the carcinomatous and sarcomatous portions. In all samples, staining for PDGFR-β was concentrated at the cell membrane and diffusely in the cytoplasm. These results indicate that many uterine sarcomas express 1 or more of the kinases targeted by imatinib mesylate and that further investigation of imatinib as a therapy for uterine sarcomas is warranted.
KW - PDGFR-β
KW - Tyrosine kinase inhibitor
KW - Uterine sarcoma
KW - c-kit
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U2 - 10.1097/01.pai.0000129057.38941.a1
DO - 10.1097/01.pai.0000129057.38941.a1
M3 - Article
C2 - 15894930
AN - SCOPUS:19444373545
VL - 13
SP - 167
EP - 170
JO - Applied Immunohistochemistry and Molecular Morphology
JF - Applied Immunohistochemistry and Molecular Morphology
SN - 1541-2016
IS - 2
ER -