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 nonossifying fibromas, and 7 cases of giant cell reparative granuloma. The results of immunohistochemical analysis of GCT showed a complete absence of TGF-beta1 expression in both mononuclear tumor cells and giant cells. Only reactive bone present within the tumor showed an intense immunoreactivity. Transforming 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 cases. Reverse transcription-polymerase chain reaction (RT-PCR) analysis performed on 10 GCTs with specific oligonucleotide primers demonstrated the presence 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 giant 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 samples from 3 nonossifying fibromas and 1 giant cell reparative granuloma confirmed the expression of the corresponding mRNA. In conclusion, according to the current data, GCT of bone can be distinguished from other giant cell-containing lesions of bone on the basis of the absence of TGF-beta1 expression at the protein level, which appears to be the result of posttranslational regulation processes.
Franchi
A
A
Department of Human Pathology and Oncology, University of Florence Medical School, Italy. Franchi@UNIFI.IT
Benvenuti
S
S
Masi
L
L
Malentacchi
C
C
Arganini
L
L
Brandi
M L
ML
Santucci
M
M
D000328:Adult; D001859:Bone Neoplasms / Q000737:chemistry* / Q000473:pathology; D001842:Bone and Bones / Q000737:chemistry* / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D018212:Giant Cell Tumor of Bone / Q000737:chemistry* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020033:Protein Isoforms / Q000032:analysis; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000235:genetics
D020033:Protein Isoforms; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta