TGF-beta isoform and receptor expression in giant cell tumor and giant cell lesions of bone

The authors examined the distribution of tumor growth factor-beta (TGF-beta ) isoforms and receptors in 35 giant cell tumor (GCT) of bone in comparison with a group of benign giant cell-containing lesions of bone, including 5 aneurysmal bone cysts, 2 cases of brown tumor of hyperparathyroidism, 3 non ossifying fibromas, and 7 cases of giant cell reparative granuloma. The res ults of immunohistochemical analysis of GCT showed a complete absence of TG F-beta1 expression in both mononuclear tumor cells and giant cells. Only re active bone present within the tumor showed an intense immunoreactivity. Tr ansforming growth factor-beta2 and TGF-beta3 were detected in the majority of cases (97.1% and 82.8%, respectively), whereas TGF-beta receptor type I (TGF-beta RI) and type II (TGF-beta RII) were diffusely expressed in all ca ses. Reverse transcription-polymerase chain reaction (RT-PCR) analysis pet- formed on 10 GCTs with specific oligonucleotide primers demonstrated the pr esence of mRNA transcripts for TGF-beta1, 2, 3, and for TGF-beta RI and RII . Quantitative measurements of TGF-beta1 in conditioned media from primary cultures of GCT showed undetectable or very low amounts of the cytokine (0- 23 pg/mL). The results of immunohistochemical analysis showed that all gian t cell-containing lesions of bone were at least focally positive for the 3 isoform of TGF-beta, with positivity present both in osteoclast-like giant cells and mononuclear cells, and diffusely positive for TGF-beta RI and RII . Reverse transcription-polymerase chain reaction analysis conducted on sam ples from 3 nonossifying fibromas and 1 giant cell reparative granuloma con firmed the expression of the corresponding mRNA. In conclusion, according t o the current data, GCT of bone can be distinguished from other giant cell- containing lesions of bone on the basis of thr absence of TGF-beta1 express ion at the protein level, which appears to be the result of posttranslation al regulation processes.