Uterine carcinosarcoma: immunohistochemical studies on tissue microarrays with focus on potential therapeutic targets.
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.
Cimbaluk
David
D
Department of Pathology, Rush University Medical Center, 1653 West Congress Parkway, Chicago, IL 60612, USA.
Rotmensch
Jacob
J
Scudiere
Jennifer
J
Gown
Allen
A
Bitterman
Pincas
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002296:Carcinosarcoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D046888:Tissue Array Analysis; D014594:Uterine Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D051546:Cyclooxygenase 2; D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit; D018719:Erb-b2 Receptor Tyrosine Kinases; D042461:Vascular Endothelial Growth Factor A