Correlation between tumor angiogenesis and invasiveness in thymic epithelial tumors☆

Abstract 

Objective: Because it is difficult to predict the behavior of thymomas on the basis of morphology alone, other methods for determining tumor aggressiveness must be explored. This study investigated the correlation between angiogenic grade and invasiveness in thymic epithelial tumors. Methods: Immunohistochemical studies of 46 surgically resected thymic epithelial tumors (18 noninvasive thymomas, 20 invasive thymomas, and 8 thymic carcinomas) were conducted. To highlight the microvessels, we used a specific monoclonal antibody against factor VIII. Expression of vascular endothelial growth factor and basic fibroblast growth factor was determined by using polyclonal antibodies. Results: Mean microvessel density readings for noninvasive thymomas, invasive thymomas, and thymic carcinomas were 4.6 ± 3.2, 12.4 ± 7.5, and 34.4 ± 16.7, respectively. Stages I, II, III, and IV of thymoma had microvessel density readings of 4.6 ± 3.2, 8.5 ± 4.3, 13.8 ± 7.7, and 22.0 ± 6.8, respectively. These findings suggest a significant correlation between microvessel density and tumor invasiveness. Vascular endothelial growth factor expression in noninvasive thymomas, invasive thymomas, and thymic carcinomas was present in 1 (5.6%) of 18, 11 (55.0%) of 20, and 5 (62.5%) of 8 patients, respectively, thereby indicating a distinct association between vascular endothelial growth factor expression and increased microvessel density. Basic fibroblast growth factor expression was present in only 8 patients. Conclusions: In patients with thymic epithelial tumors, there appears to be a significant correlation between tumor angiogenesis and invasiveness. Furthermore, our data suggests that this angiogenesis in thymic epithelial tumors might be, at least in part, dependent on vascular endothelial growth factor expression.

J Thorac Cardiovasc Surg 2002;124:493-8