Expression of osteopontin and vascular endothelial growth factor in benign and malignant bone tumors. Osteopontin (OPN), one of the major non-collagenous proteins of bone matrix, is together with vascular endothelial growth factor (VEGF) a potent angiogenic protein. In this study we determined the expression of OPN in benign and malignant bone tumors and investigated the prognostic influence of OPN expression on the outcome of osteosarcoma patients. Fifty-seven osteosarcomas and 11 osteoblastomas as well as 5 bone specimens with remodeling sites were immunohistochemically analyzed for expression of OPN and VEGF. OPN was not detected in osteoblasts of remodeling sites. Osteoblastoma osteoblasts as well as osteoclastlike giant cells and osteosarcoma mononuclear cells showed variable staining. In osteosarcomas OPN and VEGF expression correlated with each other (r=0.390, P=0.003, Spearman's test). Although osteosarcoma patients with high VEGF expression showed a trend towards shorter overall survival ( P=0.0841, log-rank test), OPN expression had no influence on patients overall or on disease-free survival. Our data indicate that expression of this protein might be upregulated in bone neoplasia. Although OPN expression correlates with VEGF expression in osteosarcomas, OPN expression does not provide predictive information about the outcome of osteosarcoma patients.