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Keywords:

  • transforming growth factor β;
  • osteosarcoma;
  • immunohistochemistry;
  • in situ hybridization;
  • RT-PCR

Abstract

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.