|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1993 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1992 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Histiocytic proliferative lesions of soft tissues show a wide spectrum of histologic features, ranging from reactive inflammatory lesions to fibrohistiocytic tumors. To elucidate the origin and characteristics of the lesions, we analyzed surgical materials of malignant fibrous histiocytoma (MFH) by single and double immunostainings, using histocytic, mesenchymal and proliferating cell markers. As controls, benign fibrous histiocytoma (dermatofibroma), and giant cell tumor of tendon sheath were studied by the same procedure.
All three types of MFH cells (spindle cells, polygonal cells and bizarre giant cells) stained positive for mesenchymal antigens (FU3 and vimentin) but did not stain for macrophage/histiocyte markers (HAM 56 and CD68). Therefore, the MFH cells may not represent true histiocytes, although they may be mesenchymalderived cells behaving as "facultative histiocytes" with superficial resemblance to actual histiocytes. Normal histiocytes in the stroma showed varying degrees
of positivity for macrophage/histiocyte antigens. Proliferating cell nuclear antigen (PCNA) and MIB-1 were expressed by all the three cell types of MFH cells. Expression of p53 protein was found in 50% of MFH, but its positivity varied greatly from tumor to tumor.
In addition, 17 MFH cell lines were analyzed by using light- and electron-microscopy, immunocytochemistry, and functional tests for Fc receptors and immunophagocytosis. Cultured MFH cells exhibited a storiform/pleomorphic pattern, corresponding to the histologic features of the primary tumors. The cells in each line displayd histiocytic functional markers such as lysosomal enzymes, Fc receptors, and immunophagocytosis. However, MFH cells expressed a mesenchymal antigen (FU3) that is distributed among perivascular cells and fibroblasts, whereas MFH cells demonstrated no positive reactions for CD15 (Leu M1) and CD14 (Leu M3) that recognize the cells of the monocyte-macrophage lineage. These findings suggest that MFH is not a tumor of true histiocytes but of "facultative histiocytes" showing both mesenchymal differentiation and histiocytic functional makers in vitro. Chromosomal analysis demonstrated complex abnormal karyotypes varying greatly among the MFH tumors examined.
By DNA flow cytometry, 76% of MFH showed aneuploidy and these tumors exhibited poor prognosis (10-year survival, 55.3%) when compared with diploid tumors (10-year suvival, 92.3%).