DNA ABERRATIONS IN THE EPITHELIAL-CELL COMPONENT OF ADAMANTINOMA OF LONG BONES

Adamantinoma of long bones is a rare malignant tumor composed of cells with epithelial characteristics in various differentiation patterns s urrounded by fibrous cells. Evidence as to whether this neoplasm shoul d be designated as an epithelial bone tumor or a biphasic sarcoma with both epithelial and mesenchymal features is lacking. In this study th e nature of the mesenchymal and epithelial components of adamantinoma was investigated by DNA flow cytometry, DNA image cytometry, p53 immun ohistochemistry, and polymerase chain reaction-based loss of heterozyg osity detection at the p53 locus. Specimens from 6 of 15 patients (40% ) analyzed by flow cytometry had an aneuploid DNA index. Image cytomet ry analysis of Feulgen-stained paraffin sections of 6 aneuploid and 2 diploid tumors revealed that aneuploid nuclei were detected in cells w ith an epithelial phenotype only, whereas all fibrous cells were diplo id. Immunohistochemistry for p53 on specimens from 25 patients reveale d moderate or strong immunoreactivity in 12 tumors (48%) restricted to the epithelial cells. Loss of heterozygosity at the p53 locus could b e confirmed in the epithelial component of an immunohistochemically p5 3-positive tumor. Additionally, sections of 7 lung metastases were stu died histologically. Only keratin-positive epithelial cells, predomina ntly in the spindle cell pattern, were present in these metastases, wh ereas the osteofibrous tissue present in the primary tumors was not de tected. These results suggest that either adamantinoma consists of a m alignant epithelial part with a reactive osteofibrous stroma or that t he malignant epithelial cells develop next to a proliferating benign f ibrous component. Additional analysis of common genetic abnormalities in the fibrous and epithelial cells of adamantinoma is therefore indic ated.