Immunohistochemical Analysis for Therapeutic Targets and Prognostic Markers in Low-Grade Endometrial Stromal Sarcoma

Abstract

To investigate potential therapeutic targets and prognostic markers for low-grade endometrial stromal sarcoma (LGESS). Thirty-nine patients with LGESS were included in this study. Using tissue microarrays, the immunohistochemical expression levels of 5 therapeutic targets (epidermal growth factor receptor, human epidermal growth factor 2, vascular endothelial growth factor receptor, platelet-derived growth factor receptor [PDGFR], and c-kit) and 3 proteins involved in cell proliferation (p16, p53, and ki67) were investigated. The associations between these targets, markers, other clinicopathological factors, disease-free survival (DFS), and overall survival (OS) were analyzed. Epidermal growth factor receptor and human epidermal growth factor 2 were not expressed in these 39 patients. Vascular endothelial growth factor receptor, PDGFR, c-kit, p16, p53, and ki67 were expressed in 10 (25.6%), 28 (71.8%), 32 (82.1%), 18 (46.2%), 4 (10.3%), and 21 (53.8%) patients, respectively. The expression of each marker was not significantly associated with other clinicopathological factors. On multivariate analysis, p53 and ki67 were associated with significantly poorer DFS and OS. The 5-year DFS rates were 88%, 46%, and 0% for the p53(-)/ki67(-) group (n = 18), p53(-)/ki67(+) group (n = 17), and p53(+)/ki67(+) group (n = 4) (P = 0.002), respectively; the 5-year OS rates were 100%, 71%, and 0%, respectively (P < 0.001). The time to recurrence was longer (P = 0.123), and more patients had distant recurrence in the p53(+)/ki67(+) group (P = 0.063). In patients with LGESS, c-kit and PDGFR were expressed in higher portions of patients, suggesting that imatinib mesylate should be investigated as a potential targeting agent. Both p53 and ki67 demonstrated strong prognostic implications, suggesting that further evaluation using these markers is required.