Investigation of New Therapeutic Targets in Undifferentiated Endometrial Sarcoma

Gynecol Obstet Invest. 2017;82(4):329-339. doi: 10.1159/000454769. Epub 2017 Jan 27.

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).

Conclusion: 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.

Keywords: Immunohistochemistry; Target therapy; Undifferentiated endometrial sarcoma.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aromatase / metabolism
  • Biomarkers, Tumor / genetics*
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Endometrium / pathology
  • ErbB Receptors / metabolism
  • Female
  • Histone Deacetylases / metabolism
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Molecular Targeted Therapy / methods
  • Proto-Oncogene Proteins c-abl / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-kit / metabolism
  • Receptor, ErbB-2 / metabolism
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Retrospective Studies
  • Sarcoma / genetics*
  • Sarcoma / pathology
  • TOR Serine-Threonine Kinases / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • WT1 Proteins / metabolism

Substances

  • Biomarkers, Tumor
  • Vascular Endothelial Growth Factor A
  • WT1 Proteins
  • WT1 protein, human
  • Aromatase
  • CYP19A1 protein, human
  • MTOR protein, human
  • EGFR protein, human
  • ERBB2 protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins c-kit
  • Receptor, ErbB-2
  • Receptors, Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-abl
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Histone Deacetylases