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, abl, 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 c-kit, abl, 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 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-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 1 or more of the kinases targeted by imatinib mesylate and that further investigation of imatinib as a therapy for uterine sarcomas is warranted.
Caudell
Jimmy J
JJ
Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030-4009, USA.
Deavers
Michael T
MT
Slomovitz
Brian M
BM
Lu
Karen H
KH
Broaddus
Russell R
RR
Gershenson
David M
DM
Ramondetta
Lois M
LM
D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D010879:Piperazines / Q000494:pharmacology; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000235:genetics*; D011743:Pyrimidines / Q000494:pharmacology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*; D012509:Sarcoma / Q000201:enzymology* / Q000473:pathology; D014594:Uterine Neoplasms / Q000201:enzymology* / Q000473:pathology
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020797:Receptor, Platelet-Derived Growth Factor beta; D016315:Proto-Oncogene Proteins c-abl