transforming-growth-factor-alpha and Giant-Cell-Tumors

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.

Topics: Adolescent; Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Bone Neoplasms; Factor XIII; Female; Giant Cell Tumors; Humans; Immunohistochemistry; Male; Middle Aged; Nuclear Proteins; Proliferating Cell Nuclear Antigen; Transforming Growth Factor alpha

Tumor specimens from 15 patients with giant cell tumor (GCT) of bone were cytogenetically analyzed. A subset of five individuals had tumor cells harvested and polyadenylated RNA isolated. Multiple Northern blots were performed utilizing radiolabeled probes for the growth factors TGF beta 1, TGF beta 2, TGF beta 3, and TGF alpha (TGF, transforming growth factor). RNAs from other types of neoplasms and nonneoplastic cells were examined as controls. The most consistent cytogenetic abnormality detected involved multiple telomeric associations (TAs), most frequently involving the terminus of the long arm of chromosome 19 (19q). Northern blot analysis revealed a consistent expression of TGF beta 1 and TGF beta 2 with an inconsistent mRNA expression for the other TGFs. There was a relative overexpression of mRNA for TGF beta 2. The gene location for TGF beta 1 is near the 19q terminus and thus it is speculated that TGF beta may play a role in the neoplastic transformation of GCT.

Topics: Adult; Blotting, Northern; Bone Neoplasms; Cell Transformation, Neoplastic; Child; Chromosomes, Human, Pair 19; Female; Gene Expression; Giant Cell Tumors; Humans; Male; Middle Aged; Radioligand Assay; Telomere; Transforming Growth Factor alpha; Transforming Growth Factor beta