Expression of transforming growth factor β isoforms in osteosarcoma variants: association of tgfβ1 with high-grade osteosarcomas
Article first published online: 19 APR 1999
Copyright © 1998 John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 185, Issue 3, pages 284–289, July 1998
How to Cite
Franchi, A., Arganini, L., Baroni, G., Calzolari, A., Capanna, R., Campanacci, D., Caldora, P., Masi, L., Brandi, M. L. and Zampi, G. (1998), Expression of transforming growth factor β isoforms in osteosarcoma variants: association of tgfβ1 with high-grade osteosarcomas. J. Pathol., 185: 284–289. doi: 10.1002/(SICI)1096-9896(199807)185:3<284::AID-PATH94>3.0.CO;2-Z
- Issue published online: 19 APR 1999
- Article first published online: 19 APR 1999
- Manuscript Accepted: 9 JAN 1998
- Manuscript Received: 2 MAY 1997
- Italian Association of Cancer Research (AIRC)
- transforming growth factor β;
- in situ hybridization;
Studies on osteosarcoma cell lines point to the potential importance of transforming growth factor β (TGFβ) as an autocrine factor which controls the growth of human osteosarcomas. To define further the role of TGFβ isoforms in these neoplasms, a series of 27 osteosarcomas was studied using immunohistochemical, mRNA in situ hybridization, and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. All 14 central high-grade osteosarcomas, two telangiectatic osteosarcomas, and one high-grade surface osteosarcoma showed cytoplasmic immunoreactivity for TGFβ1, -2, and -3. The expression of TGFβ1 was moderate or diffuse in 14 cases (82·3 per cent), while low expression was detected in only three cases (17·7 per cent). For TGFβ2 and -3, only moderate or diffuse staining was observed. Low-grade parosteal and periosteal osteosarcomas showed low or undetectable levels of TGFβ1, while TGFβ2 and -3 were moderately or diffusely expressed. Finally, three dedifferentiated parosteal osteosarcomas were diffusely positive for TGFβ1, -2, and -3 in the high-grade component, while in the low-grade component, available for analysis in two of these cases, TGFβ1 was demonstrated in a few neoplastic cells, and TGFβ2 and -3 maintained a diffuse distribution. Statistical analysis of these data showed that high-grade osteosarcomas had a significantly higher expression of TGFβ1 than low-grade osteosarcomas, while levels of TGFβ2 and -3 were comparable in the two groups (p<0·001; p=0·3; p=0·3, respectively; Fisher's exact test). Similarly, mRNA levels of TGFβ1 detected by in situ hybridization were significantly higher (p=0·04, Fisher's exact test) in high-grade osteosarcoma variants, while no differences were found for TGFβ2 and -3 mRNA (p=1·0; p=0·2, respectively; Fisher's exact test). In addition, mRNA analysis performed by RT-PCR in seven cases (five high-grade and two low-grade osteosarcomas) confirmed the presence of high levels of TGFβ1 in high-grade osteosarcomas, while low-grade tumours had low or absent mRNA expression. In conclusion, this positive association suggests that TGFβ1 may be involved in determining the aggressive clinical behaviour of high-grade osteosarcomas. © 1998 John Wiley & Sons, Ltd.