Immunohistochemical analysis of nm23 protein expression in malignant bone tumors. Expression levels of nm23 protein in 72 malignant bone tumors comprising 41 osteosarcomas, 22 chondrosarcomas, 6 Ewing's sarcomas, and 2 malignant fibrous histiocytomas were examined immunohistochemically, using anti-nm23 protein polyclonal antibody, and compared with 51 cases of benign bone tumors or tumor-like lesions. Malignant bone tumors showed significantly higher nm23 protein expression than benign bone tumors or tumor-like lesions (P < 0.0001). In chondrosarcoma, nm23 expression increased in high-grade tumors (grade I versus grade II and III: P = 0.0229). In the cases of osteosarcoma, however, grade IV osteosarcomas showed decreased expression of nm23 compared with grade III tumors (P = 0.0122). There was no significant relationship between nm23 expression and histological type. nm23 expression had no correlation with metastatic potential in osteosarcoma, although the therapy was not uniform in our cases. Furthermore, in 6 cases of osteosarcoma and 1 case of Ewing's sarcoma, there was no clear tendency for a decrease of nm23 in the metastatic sites compared with primary sites, as reported in breast cancer. These results showed that, in contrast to reports on breast cancer and experimental models, nm23 protein expression in human bone tumors may be associated with malignant potentiality, except in cases of osteosarcoma.