title: Immunohistochemical analysis for therapeutic targets and prognostic markers in low-grade endometrial stromal sarcoma.
abstract: OBJECTIVE
  To investigate potential therapeutic targets and prognostic markers for low-grade endometrial stromal sarcoma (LGESS).
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Jeong-Yeol
authors.initials: JY
authors.lastname: Park
authors.forename: Kyu-Rae
authors.initials: KR
authors.lastname: Kim
authors.forename: Joo-Hyun
authors.initials: JH
authors.lastname: Nam
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D060787:Neoplasm Grading; D011379:Prognosis; D018203:Sarcoma, Endometrial Stromal / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor