Transforming growth factor alpha and CD68 immunoreactivity in giant cell tumours of bone: a study on the nature of stromal and giant cells, and their interrelations.

To clarify the nature of neoplastic cells, 17 giant cell tumours of bone were studied histologically and immunohistochemically. L1 antigen and S-100 protein were not detected in the tumour giant cells and stromal cells, although present in non-neoplastic macrophages. The giant cells in all the lesions, some stromal cells, and osteoclasts in the normal bone showed CD68 and transforming growth factor alpha (TGF alpha) immunoreactivity. Fibrohistiocytic antigen, factor XIIIa, was expressed in large numbers of stromal cells in all lesions. Some stromal cells expressed alpha-smooth muscle actin and osteocalcin. These immunohistochemical results suggested that the stromal cells of giant cell tumours of bone showed histiocytic and occasional myofibroblastic and osteoblastic differentiation. Proliferating cell nuclear antigen was demonstrated in the nuclei of the stromal cells only, indicating that these were the sole proliferating elements. TGF alpha produced by the giant cells and some stromal cells may play a role as a mediator for the attraction and/or proliferation of the precursor cells, and may suppress the activity of osteoblastic stromal cells, resulting in restricted bone formation in giant cell tumours.