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Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
Investigation of New Therapeutic Targets in Undifferentiated Endometrial Sarcoma
Min-Hyun Baek1, Jeong-Yeol Park, Chae Chun Rhim
1Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
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.
Insights
Undifferentiated endometrial sarcoma (UES) shows high expression of VEGF, AKT1, CYP19A1, and HDACs. These markers, particularly CYP19A1 and HDAC6, are linked to recurrence, suggesting potential therapeutic targets for this rare uterine sarcoma.
Area of Science:
- Oncology
- Molecular Pathology
Background:
- Undifferentiated endometrial sarcoma (UES) is a rare uterine sarcoma with no established treatment consensus.
- UES exhibits an aggressive clinical course and poor survival outcomes.
Purpose of the Study:
- To investigate potential new therapeutic targets in UES.
- To identify molecular markers associated with UES progression and recurrence.
Main Methods:
- Immunohistochemical analysis of 10 UES patient tissue microarrays.
- Assessed expression of VEGF, c-KIT, c-ABL, PDGFR, AKT1, mTOR, EGFR, HER2, WT1, CYP19A1, and HDAC series.
Main Results:
- High expression of VEGF, AKT1, HDAC2/7 (80%), CYP19A1, HDAC6 (90%), and HDAC1/4/8 (100%) was observed.
- Strong CYP19A1 and HDAC6 expression correlated with distant recurrence (p=0.030).
- WT1 expression indicated a more advanced stage (p=0.033). Adjuvant therapy improved survival (p=0.003).
Conclusions:
- VEGF, AKT1, CYP19A1, and HDAC series (HDAC1-8) are frequently overexpressed in UES.
- These markers represent promising therapeutic targets for UES.
- Targeting these pathways may improve outcomes for patients with undifferentiated endometrial sarcoma.
