ANGIOGENESIS AND ANGIOGENIC GROWTH FACTORS IN WILMS TUMOR

Abstract

PURPOSE: Angiogenesis, that is new blood vessel formation, is a prerequisite for growth and metastasis of solid tumors. This study was undertaken to quantify tumor capillaries, investigate immunohistochemical expression and measure serum concentrations of angiogenic growth factors in patients with Wilms tumor. MATERIALS AND METHODS: The hospital records of 33 patients were reviewed and new slides were stained for the endothelial cell marker CD31. Capillaries were quantified in the most vascularized part of the tumor (hot spot) and in the whole slide. New slides were stained immunohistochemically for the angiogenic growth factors angiogenin, basic fibroblast growth factor (bFGF), transforming growth factor alpha, transforming growth factor beta1-3, tumor necrosis factor alpha and vascular endothelial growth factor (VEGF), and their immunoreactivity was quantified. Pretreatment serum samples from 14 patients and 56 healthy control children were analyzed using enzyme-linked immunosorbent assay kits for angiogenin, basic fibroblast growth factor, epidermal growth factor, hepatocyte growth factor, tumor necrosis factor alpha and VEGF. RESULTS: Logistic regression analysis and Kaplan-Meier estimates showed that quantifications based on the tumor hot spot had a significant impact on survival probability (p <0.05). The tumor hot spot counts were highest in the blastemal compartment. Levels of hepatocyte growth factor and VEGF in serum were 3 times higher than those in controls (p <0.01). CONCLUSIONS: Although the sample size is small in this study, the results imply that angiogenesis in Wilms tumor is driven by angiogenic growth factors, and that intratumoral capillary quantification and determinations of serum levels of angiogenic growth factors may be of clinical value.