Detection of Angiogenesis Activity in Malignant Bladder Tissue and Cells

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Abstract
Neoplastic and nonneoplastic mammalian urothelium was tested for angiogenesis activity in the rabbit iris assay. Tiny fragments of tisue were placed on a rabbit''s iris and observed through a slit lamp stereoscope for as long as 4 days after implantation. Angiogenesis activity was demonstrated either by the appearance of new capillary growth or, following an injection of fluorescein, by a green fluorescence around an implant. Capillary proliferation was stimulated by 99% of the specimens containing malignant urothelium, while only 9% of normal urothelial specimens had this effect (P < 0.001). Cells grown in vitro were similarly tested for angiogenesis by implanting 1 mm fragments of collagen coated either with malignant or normal cells. A total of 92% of the specimens covered with neoplastic cells induced angiogenesis, while only 15% of the implants covered by normal cells caused this response (P < 0.001). Benign reversible hyperplasia was induced in a rabbit bladder by systemic administration of cyclophosphamide, and an angiogenic response could not be detected in a small number of specimens. The results suggest that angiogenesis activity may be a reliable method for distinguishing between benign and malignant bladder tissue.