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Published on: November 28, 2010
Uterine carcinosarcoma: immunohistochemical studies on tissue microarrays with focus on potential therapeutic targets
David Cimbaluk1, Jacob Rotmensch, Jennifer Scudiere
1Department of Pathology, Rush University Medical Center, 1653 West Congress Parkway, Chicago, IL 60612, USA.
Objective:
Carcinosarcoma of the uterus is a highly aggressive tumor containing both malignant epithelial and spindle (mesenchymal) components. Because of their rarity and poor clinical outcome, investigations into the expression of potential therapeutic targets are limited. The aim of this study was to determine the expression of therapeutic targets in both the epithelial and spindle (mesenchymal) components in 30 carcinosarcomas using tissue microarrays, for potential treatment strategy.
Methods:
We collected formalin-fixed, paraffin-embedded tissue blocks of carcinosarcoma of the uterine corpus resected from 30 patients who had undergone total abdominal hysterectomies at our institution between 1985 and 2005 (ages 38-83 years, mean 65.9 years). All hematoxylin-eosin stained sections from each tumor were reviewed to confirm the pathologic diagnosis. Two tissue cores from the paraffin-embedded tissue blocks were constructed into a tissue microarray. Sections were stained with monoclonal antibodies against HER-2, VEGF, c-KIT, COX-2, and EGFR. Unequivocal staining of at least 5% tumor cells was considered positive. HER-2 amplification was also examined by fluorescence in situ hybridization (FISH) in 2 cases.
Results:
In the epithelial component, expression of HER-2, VEGF, c-KIT, COX-2, and EGFR were detected in 2 (6%), 30 (100%), 0 (0%), 21 (70%), and 9 (30%) cases, respectively, whereas these expressions in the spindle (mesenchymal) component were detected in 0 (0%), 28 (93%), 0 (0%), 5 (16%), and 20 (67%) cases, respectively. By FISH, one of the two cases with HER-2 expression showed gene amplification (2.62).
Conclusions:
VEGF is strongly expressed in both the epithelial and spindle (mesenchymal) components of uterine carcinosarcoma. This result warrants further study to evaluate the possible role of anti-angiogenic agents in cancer therapy for patients with uterine carcinosarcomas. The expression patterns of COX-2 and EGFR differed between the epithelial and spindle (mesenchymal) components. HER-2 and c-KIT are poor therapeutic targets for uterine carcinosarcomas.
Insights
Vascular Endothelial Growth Factor (VEGF) is highly expressed in uterine carcinosarcoma, suggesting anti-angiogenic agents may be effective. HER-2 and c-KIT are not viable therapeutic targets for this aggressive cancer.
Area of Science:
- Oncology
- Gynecologic Oncology
- Molecular Pathology
Background:
- Uterine carcinosarcoma is a rare, aggressive malignancy with poor prognosis.
- Limited research exists on therapeutic targets due to rarity and poor outcomes.
- Understanding target expression is crucial for developing effective treatment strategies.
Purpose of the Study:
- To investigate the expression of potential therapeutic targets, including HER-2, VEGF, c-KIT, COX-2, and EGFR.
- To compare target expression in both epithelial and spindle (mesenchymal) components of uterine carcinosarcomas.
- To inform potential treatment strategies for uterine carcinosarcoma.
Main Methods:
- Utilized tissue microarrays from 30 uterine carcinosarcoma cases.
- Performed immunohistochemical staining for HER-2, VEGF, c-KIT, COX-2, and EGFR.
- Assessed HER-2 amplification using fluorescence in situ hybridization (FISH) in select cases.
Main Results:
- VEGF showed high expression (100% epithelial, 93% spindle).
- COX-2 and EGFR expression patterns differed between epithelial and spindle components.
- HER-2 and c-KIT expression was minimal (6% and 0% in epithelial, 0% and 0% in spindle, respectively).
Conclusions:
- Strong VEGF expression suggests potential efficacy of anti-angiogenic therapies.
- COX-2 and EGFR show differential expression, indicating potential for targeted therapy based on component.
- HER-2 and c-KIT appear to be poor therapeutic targets for uterine carcinosarcomas.
