PDGFR and c-Kit as therapeutic targets and p53 and ki67 as prognostic markers for low-grade endometrial stromal sarcoma.

Abstract

e15559 Background: To determine whether proteins targeted by currently available targeted agents are expressed in low-grade endometrial stromal sarcoma (LGESS) and to test these can be prognostic markers for LGESS. Methods: Of 48 patients with LGESS, 39 patients whose paraffin blocks of tumor in hysterectomy specimen were available were included. Using tissue microarrays, immunohistochemical expression of five therapeutic targets (EGFR, HER-2/neu, VEGFR, PDGFR and c-kit), and three proteins involved in cell proliferation (p16, p53, and ki67) were investigated. The association of these targets and markers with other clinopathologic factors and disease-free (DFS) and overall survival (OS) were analyzed. Results: EGFR and HER-2/neu were not expressed in 39 patients. VEGFR, PDGFR, c-kit, p16, p53, and ki67 was expressed in 10 (25.6%), 28 (71.8%), 32 (82.1%), 18 (46.2%), 4 (10.3%), and 21 (53.8%) patients, respectively. Expression of each marker was not significantly associated with other clinicopathologic factors. In multivariate analysis, p53 and ki67 were associated with significantly poorer DFS and OS. The 5-year DFS was 88%, 46% and 0% for p53(-)/ki67(-) group (n=18), p53(-)/ki67(+) group (n=17), and p53(+)/ki67(+) group (n=4), and the 5-year OS was 100%, 71%, and 0%, respectively. The time interval to recurrence was longer and more patients had distant recurrence in p53(+)/ki67(+) group. Conclusions: In patients with LGESS, c-kit and PDGFR were expressed in high portion of patients, suggesting imatinib mesylate may be a potential target agent. Both p53 and ki67 had strong prognostic implication, suggesting the combination of these proteins may be used as a prognostic marker.