Relation between Histological Intensity of Transforming Growth Factor-β Isoforms in Human Osteosarcoma and the Rate of Lung Metastasis

抄録

Eventhough adjuvant chemotherapy has improved the 5-year survival rate of osteosarcoma patients, a significant percentage of patients eventually die from lung metastasis. Since transforming growth fartor-β (TGF-β) has been demonstrated to be related to the tumor progression, we investigated the clinical implications of the presence of TGF-β isoforms in 16 human osteosarcoma tissue. There were 10 males and 6 females with a mean age of 20.8 years of age (range, 8 to 57 years). Biopsied specimen before chemotherapy was fixed in 10% formalin, demineralized and followed by paraffin embedding. The locations of tumor included femur (10), tibia (3), humerus (1), fibula (1), and ilium (1). Histologic subtypes included osteoblastic (11), chondroblastic (2), and fibroblastic (3). All patients were followed for a minimum of 1 year (range 12 to 44 months) or to the development of lung metastasis. Five patients (31.3%) developed subsequent lung metastasis during the follow up. We used immunohistochemistry technique to investigate the presence of the TGF-β isoforms in osteosarcoma tissue and its relationship to the subsequent pulmonary metastasis. The results showed the presence of one or more TGF-β isoforms in tumor cells in osteosarcoma tissues (13 of 16, 81.3%) in all of the subtypes. However, minimal presence of TGF-β isoforms was shown in the tumor bone matrix. The expression of TGF-β1 or TGF-β3 isoforms was associated with a higher rate of subsequent lung metastasis (p<0.05, chi-square test). Further research is warranted to determine the utility of routine TGF-β analysis in the clinical practice.