Angiogenesis and expression of angiogenic agents in uterine and ovarian carcinosarcomas

Abstract

Carcinosarcomas of the female genital tract are a heterogeneous group of aggressive malignant neoplasms characterized by poor prognosis that contain elements expressing both carcinomatous and sarcomatous characteristics. In this study specimens from 25 patients were treated with labeled antibodies to vascular endothelium (FVIII), and to vascular endothelial growth factor (VEGF) for analysis of angiogenesis, and to vascular endothelial growth factor receptor 3 (VEGFR-3) for analysis of lymphangiogenesis, in 11,099 vessels. Automated quantitative image analysis was used and the results were compared with clinical data. Microvessel density increased from a median value of 18.32 vessels/mm(2) in non-neoplastic stroma to 131.25 vessels/mm(2) in neoplasms. In areas around tumor islets expressing predominantly epithelial carcinomatous characteristics, microvessel density was increased three-fold compared with the islets themselves. Vessels were arranged in a garland-type pattern, or in bursts, and they exhibited directional angiogenesis. Clinical indicators of poor survival were high tumor stage (p=0.002) and age above 65 (p=0.0769). A high number of small vessels (16-300 mum(2) in cross-sectional area) predicted poor survival (p=0.0149), and more so in tumors exhibiting predominantly sarcomatous characteristics (p=0.0087). Tumor tissue area above the median exhibiting VEGF expression was also a sign of poor survival (p=0.0267), as was an area of positive staining for VEGFR-3 exceeding the median (p=0.00487). In this study, active angiogenesis (increased number of vessels, variable in shape and exhibiting decreased antibody staining intensity) was a distinct feature of carcinosarcomas, its extent and distribution depending upon neoplasm morphology. Increased vessel numbers and increased VEGF and VEGFR-3 expression indicated poor survival.