ABSTRACT
Osteoblastoma and osteoid osteoma together are the most frequent benign bone-forming tumor, arbitrarily separated by size. In some instances, it can be difficult to differentiate osteoblastoma from osteosarcoma. Following our recent description of FOS gene rearrangement in these tumors, the aim of this study is to evaluate the value of immunohistochemistry in osteoid osteoma, osteoblastoma, and osteosarcoma for diagnostic purposes. A total of 337 cases were tested with antibodies against c-FOS: 84 osteoblastomas, 33 osteoid osteomas, 215 osteosarcomas, and 5 samples of reactive new bone formation. In all, 83% of osteoblastomas and 73% of osteoid osteoma showed significant expression of c-FOS in the osteoblastic tumor cell component. Of the osteosarcomas, 14% showed c-FOS expression, usually focal, and in areas with severe morphologic atypia which were unequivocally malignant: 4% showed more conspicuous expression, but these were negative for FOS gene rearrangement. We conclude that c-FOS immunoreactivity is present in the vast majority of osteoblastoma/osteoid osteoma, whereas its expression is usually focal or patchy, in no more than 14% of osteosarcoma biopsies. Therefore, any bone-forming tumor cases with worrying histologic features would benefit from fluorescence in situ hybridization analysis for FOS gene rearrangement. Our findings highlight the importance of undertaking a thorough assessment of expression patterns of antibodies in the light of morphologic, clinical, and radiologic features.
Subject(s)
Biomarkers, Tumor/analysis , Bone Neoplasms/chemistry , Osteoblastoma/chemistry , Osteoma, Osteoid/chemistry , Proto-Oncogene Proteins c-fos/analysis , Adolescent , Adult , Biomarkers, Tumor/genetics , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Child , Child, Preschool , Diagnosis, Differential , England , Female , Gene Rearrangement , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Male , Middle Aged , Osteoblastoma/genetics , Osteoblastoma/pathology , Osteoma, Osteoid/genetics , Osteoma, Osteoid/pathology , Predictive Value of Tests , Proto-Oncogene Proteins c-fos/genetics , Switzerland , Young AdultABSTRACT
Osteonectin (ON), a 32,000-kd glycoprotein involved in the early steps of mineralization of skeletal tissue, is a recognized differentiation marker of normal osteogenic cells. The expression of ON was evaluated in vitro and in tissue sections by the polyclonal antibody bON II. In different cell cultures immunocytochemistry and molecular biology displayed a nonspecific reaction for the antibody, which showed itself to be useless for the in vitro identification of cells of the osteoblastic lineage. The diagnostic use of bON II antibody was investigated by immunohistochemistry on a series of osteogenic and nonosteogenic bone tumors. A strongly positive stain of the entire neoplastic component of osteosarcoma and osteoblastoma and a weaker stain of the mononuclear component of giant cell tumor and chondroblastoma were observed. On the other hand, stains for chondrosarcoma, Ewing's sarcoma, fibrosarcoma, malignant fibrous histiocytoma, and brown tumor from hyperparathyroidism were entirely negative. Our results indicate that ON may be helpful in the histologic diagnosis of bone tumors, particularly in differentiating small cell osteosarcoma from other small round cell tumors.
Subject(s)
Biomarkers, Tumor/analysis , Bone Neoplasms/chemistry , Bone Neoplasms/diagnosis , Osteoma, Osteoid/chemistry , Osteoma, Osteoid/diagnosis , Osteonectin/analysis , Osteosarcoma/chemistry , Osteosarcoma/diagnosis , Blotting, Northern , Bone Neoplasms/pathology , Humans , Immunohistochemistry , Microscopy, Electron , Microscopy, Immunoelectron , Osteoma, Osteoid/pathology , Osteonectin/genetics , Osteonectin/metabolism , Osteosarcoma/pathology , RNA, Neoplasm/analysis , RNA, Neoplasm/genetics , Tumor Cells, Cultured/chemistry , Tumor Cells, Cultured/metabolism , Tumor Cells, Cultured/pathologyABSTRACT
Osteoid osteoma is a tumour of bone characterised by pain which is relieved by aspirin and nonsteroidal anti-inflammatory drugs. Very high levels of prostaglandins have been found in the lesion. In five patients with osteoid osteoma, prostaglandin E2 (PGE2) and prostacyclin (PGI2) synthesis in the nidus yielded 1155.6 +/- 496.5 (mean +/- SD) and 245.2 +/- 89.8 pg/mg respectively, values which are 33 and 26 times higher than in fragments of normal bone. The sclerotic bone around the nidus produced both prostaglandins at the same rate as normal bone. In three patients the excretion rate of the major urinary metabolite of systemic PGI1 was reduced to 50% one month after removal of the tumour. The urinary excretion rate of 6-keto-PGF1 alpha, reflecting intrarenal PGI2 synthesis, was not changed after operation. These results offer new insight into the pain mechanism in osteoid osteoma.
