title: Investigation of New Therapeutic Targets in Undifferentiated Endometrial Sarcoma.
abstract: BACKGROUND
  Undifferentiated endometrial sarcoma (UES) is a very rare subtype of uterine sarcoma, which has no consensus on the treatment. We investigated the expression of potential new therapeutic targets in UES to improve its aggressive clinical course and poor survival outcome.
  
  
  METHODS
  The immunohistochemical expressions of vascular endothelial growth factor (VEGF), c-KIT, c-ABL, platelet derived growth factor receptor (PDGFR), protein kinase B (AKT1), mammalian target of rapamycin, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER2), Wilms tumor (WT1), aromatase inhibitor (CYP19A1), and histone deacetylase (HDAC) series in 10 UES patients were assessed using tissue microarrays.
  
  
  RESULTS
  Strongly positive immunoreactivities were observed for VEGF, AKT1, and HDAC2/7 in 8 (80.0%) tumors; for CYP19A1 and HDAC6 in 9 (90%) tumors; and for HDAC1/4/8 in 10 (100%) tumors. Strong expression of CYP19A1 and HDAC6 was associated with distant recurrence (p = 0.030, both), and expression of WT1 indicated a more advanced stage (p = 0.033). UES treated with adjuvant therapy showed better disease-free and overall survivals (both 0 vs. 33.3%, p = 0.003).
  
  
  CONCLUSIONS
  VEGF, AKT1, CYP19A1, and the HDAC1/2/4/6/7/8 series show an especially high frequency of strong immunoreactivity in UES and can be considered potential therapeutic targets.
authors.affiliation: Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Min-Hyun
authors.initials: MH
authors.lastname: Baek
authors.forename: Jeong-Yeol
authors.initials: JY
authors.lastname: Park
authors.forename: Chae Chun
authors.initials: CC
authors.lastname: Rhim
authors.forename: Jong-Hyeok
authors.initials: JH
authors.lastname: Kim
authors.forename: Yangsoon
authors.initials: Y
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; D001141:Aromatase / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D004717:Endometrium / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D012189:Retrospective Studies; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D025721:WT1 Proteins / Q000378:metabolism
chemical_list: D001141:Aromatase; D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D006655:Histone Deacetylases; D016315:Proto-Oncogene Proteins c-abl; D051057:Proto-Oncogene Proteins c-akt; D019009:Proto-Oncogene Proteins c-kit; D018719:Erb-b2 Receptor Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A; D025721:WT1 Proteins; C583751:WT1 protein, human; C561410:CYP19A1 protein, human; C546842:MTOR protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C494918:AKT1 protein, human
keywords: Immunohistochemistry; Target therapy; Undifferentiated endometrial sarcoma