RESEARCHTGF-β Isoform and Receptor Expression in Giant Cell Tumor and Giant Cell Lesions of BoneFranchi, Alessandro M.D.; Benvenuti, Susanna B.Sc.; Masi, Laura M.D., Ph.D.; Malentacchi, Cecilia B.Sc.; Arganini, Luisa B.Sc.; Brandi, Maria Luisa M.D., Ph.D.; Santucci, Marco M.D. Author Information From the Department of Human Pathology and Oncology (A.F., L.A., M.S.), Endocrine Unit (S.B., L.M., M.L.B.), and Human Genetics Unit (C.M.), Department of Clinical Physiopathology, University of Florence Medical School, Florence, Italy. Manuscript received August 8, 2000; accepted November 20, 2000. This study was supported by grants from the Italian Association for Cancer Research (AIRC) and the Italian Ministry of University, Scientific and Technologic Research. Address correspondence and reprint requests to Dr. Alessandro Franchi, Istituto di Anatomia e Istologia Patologica, Viale G.B. Morgagni 85, 50134 Firenze, Italy. E-mail: [email protected] Applied Immunohistochemistry & Molecular Morphology: June 2001 - Volume 9 - Issue 2 - p 170-175 Buy Abstract The authors examined the distribution of tumor growth factor-β (TGF-β) 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-β1 expression in both mononuclear tumor cells and giant cells. Only reactive bone present within the tumor showed an intense immunoreactivity. Transforming growth factor-β2 and TGF-β3 were detected in the majority of cases (97.1% and 82.8%, respectively), whereas TGF-β receptor type I (TGF-β RI) and type II (TGF-β 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-β1, 2, 3, and for TGF-β RI and RII. Quantitative measurements of TGF-β1 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-β, with positivity present both in osteoclast-like giant cells and mononuclear cells, and diffusely positive for TGF-β 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- β1 expression at the protein level, which appears to be the result of posttranslational regulation processes. Copyright 2001 Wolters Kluwer Health, Inc. All rights reserved.