IMMUNOHISTOCHEMICAL DETECTION OF BONE MORPHOGENETIC PROTEINS IN BONE AND SOFT-TISSUE SARCOMAS

Background. Bone morphogenetic proteins (BMPs) are potent inducers of bone formation. Functional and immunohistochemical studies have identi fied BMPs in a subset of osteosarcomas. In the present study, the auth ors extend the analysis of BMP expression to other bone and soft tissu e sarcomas. Methods. Monoclonal antibody AbH3b2/17 against human BMP-2 and BMP-4 was used in avidin-biotin-immunoperoxidase assays with froz en sections of bone tumors (71 specimens), soft tissue sarcomas (69 sp ecimens), and normal tissues. Results. Among bone tumors, BMP was dete cted in osteosarcomas (17 of 29 samples), malignant fibrous histiocyto mas (MFHs) (6 of 6), and the spindle cell sarcomatous components of sp indle cell (dedifferentiated) chondrosarcomas (4 of 4), but not in con ventional chondrosarcomas (0 of 10) or Ewing's sarcomas (0 of 14). His tologic subtypes of osteosarcoma differed for BMP expression, with 8 o f 9 fibrohistiocytic, 9 of 13 osteoblastic, and 0 of 5 chondroblastic lesions showing immunostaining. In all BMP-positive bone tumors, immun ostaining was localized in the cytoplasm of primitive mesenchymal cell s, with little or no staining in tumor matrix and more mature osteobla stic/chondrocytic cells. Among soft tissue sarcomas, MFHs (11 of 12), liposarcomas (5 of 11), leiomyosarcomas (3 of 9), and malignant schwan nomas (3 of 8) showed cytoplasmic BMP immunostaining. Synovial sarcoma s (0 of 9), rhabdomyosarcomas (0 of 8), and fibrosarcomas (0 of 7) wer e BMP-negative. All normal human tissues tested, including the tissues of a 16-week-old fetus, lacked BMP immunoreactivity. Conclusions. Bon e morphogenetic protein is expressed in a subset of osteosarcomas, a h igh proportion of MFHs of bone and soft tissue, and in spindle cell ch ondrosarcomas. In these tumors, BMP is localized predominantly to the cytoplasm of malignant cells with primitive mesenchymal features; no o r little BMP is detected in the more differentiated elements of bone a nd soft tissue sarcomas. Different histologic types of bone and soft t issue sarcomas may mimic discrete stages of mesenchymal differentiatio n as defined by BMP expression and histologic criteria.