HISTOLOGICAL AND IMMUNOHISTOCHEMICAL DIVERSITIES, AND PROLIFERATIVE ACTIVITY AND GRADING IN OSTEOSARCOMAS

To examine the differentiation and proliferative activity of tumor cel ls, 30 osteosarcomas, including osteoblastic, chondroblastic, fibrobla stic, malignant fibrous histiocytoma-libe, telangiectatic, giant tell- rich, low-grade central, and epithelioid types, were studied immunohis tochemically. A variable number of tumor cells in all cases showed ost eocalcin immunoreactivity. In four preparations of the frozen sections , osteoblastic, fibroblastic, and chondroblastic tumor cells were posi tive for bone-type alkaline phosphatase antibody 2D3. S-100 protein im munoreactivity was found not only in seven tumors of the chondroblasti c type, but also in four of nine osteoblastic tumors and each of the l ow-grade central, giant cell-rich, and epithelioid types. A histiocyti c marker, CD68, was negative for tumor cells in all cases. Some cells of 17 tumors were positive for desmin and/or alpha-smooth muscle actin ; this was regarded as an indication of myofibroblastic differentiatio n. Tumor cells of the epithelioid type and those of two osteoblastic t umors expressed cytokeratin (CAM5.2) and epithelial membrane antigen. Proliferating-cell nuclear antigen (PCNA) reactivity was found in the cell nuclei of 22 tumors, most of which were high grade. Many cells in sex high-grade tumors also showed the nuclear staining for p53 protei n. Of these tumors, PCNA and p53 positivities tended to be more numero us in osteoblastic tells, atypical spindle-shaped, and bizarre giant c ells than in well-developed chondroid cells. From these findings, oste osarcomas are concluded to be composed basically of osteoblastic cells , that are indispensable Tor diagnosis of osteosarcomas, with a variab le number of chondroblastic, myofibroblastic, and, rarely. epithelioid cells, and this manifold cellular differentiation corresponds to the histological and clinical diversities. The osteoblastic, fibro- or myo fibroblastic, and undifferentiated cells mainly participate in prolife ration of osteosarcomas. The p53 gene alterations may play a part in t he neoplastic transformation and proliferation of osteosarcomas.