Tumor angiogenesis in pheochromocytomas and paragangliomas

Background. Angiogenesis correlates with growth and likely metastases in several tumors. To determine whether it has a similar role in pheochromocytomas, immunohistochemical staining of factor VIII was done on the tumor tissue of 42 patients. Methods. Formalin-fixed, paraffin-embedded tissue was obtained from 29 women and 13 men with 24 primary adrenal and 18 extraadrenal pheochromocytomas. Patients were divided into two groups. Group 1 included 32 patients with benign pheochromocytomas, and group 2 included 10 patients with malignant tumors evidenced by capsular or vascular invasion (six), liver metastases (three), or periaortic lymph node metastases (one). Blood vessels highlighted by factor VIII staining of endothelial cells with labeled streptavidin-biotin were counted under light microscopy. Mean vessel count within a 10 mm² micrometer disk was calculated under x100, x200, and x400 magnification fields. Results. There were no significant differences in patient age or clinical symptoms between the groups. The mean tumor size in group 2 of 8.8 ± 5.3 cm was larger than the mean of 4.8 ± 2.8 cm in group 1 (p<0.005). The mean counts of vessels in the x100, x200, and x400 magnification fields were 102 ± 48, 40 ± 18, and 19 ± 9 in group 1, and 203 ± 77, 73 ± 28, and 37 ± 15 in group 2. The number of blood vessels in group 2 was significantly higher than in group 1 (p<0.001) in each studied field. Conclusions. In this study the number of tumor blood vessels correlated with the invasive behavior of pheochromocytomas. Tumor angiogenesis may be useful in determining the likelihood of malignant behavior in pheochromocytomas.