Histological and immunohistochemical diversities, and proliferative activity and grading in osteosarcomas.
To examine the differentiation and proliferative activity of tumor cells, 30 osteosarcomas, including osteoblastic, chondroblastic, fibroblastic, malignant fibrous histiocytoma-like, telangiectatic, giant cell-rich low-grade central, and epithelioid types, were studied immunohistochemically. A variable number of tumor cells in all cases showed osteocalcin immunoreactivity. In four preparations of the frozen sections, osteoblastic, fibroblastic, and chondroblastic tumor cells were positive for bone-type alkaline phosphatase antibody 2D3. S-100 protein immunoreactivity was found not only in seven tumors of the chondroblastic type, but also in four of nine osteoblastic tumors and each of the low-grade central, giant cell-rich, and epithelioid types. A histiocytic 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 differentiation. Tumor cells of the epithelioid type and those of two osteoblastic tumors 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 six high-grade tumors also showed the nuclear staining for p53 protein. Of these tumors, PCNA and p53 positivities tended to be more numerous in osteoblastic cells, atypical spindle-shaped, and bizarre giant cells than in well-developed chondroid cells. From these findings, osteosarcomas are concluded to be composed basically of osteoblastic cells, that are indispensable for diagnosis of osteosarcomas, with a variable number of chondroblastic, myofibroblastic, and, rarely, epithelioid cells, and this manifold cellular differentiation corresponds to the histological and clinical diversities. The osteoblastic, fibro- or myofibroblastic, and undifferentiated cells mainly participate in proliferation of osteosarcomas. The p53 gene alterations may play a part in the neoplastic transformation and proliferation of osteosarcomas.
Hasegawa
T
T
First Department of Pathology, University of Tokushima School of Medicine, Japan.
Hirose
T
T
Seki
K
K
Hizawa
K
K
Ishii
S
S
Wakabayashi
J
J
D000469:Alkaline Phosphatase / Q000378:metabolism; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006801:Humans; D007158:Immunologic Techniques; D015675:Osteocalcin / Q000378:metabolism; D012516:Osteosarcoma / Q000175:diagnosis* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D003598:Cytoskeletal Proteins; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D015675:Osteocalcin; D000469:Alkaline Phosphatase