EXPRESSION OF TRANSFORMING-GROWTH-FACTOR-BETA (TGF-BETA) ISOFORMS IN OSTEOSARCOMAS - TGF-BETA-3 IS RELATED TO DISEASE PROGRESSION

BACKGROUND. Transforming growth factor-beta (TGF-beta) is a multipoten t growth factor affecting development, homeostasis, and tissue repair. In addition, increased expression of TGF-beta has been reported in di fferent malignancies, suggesting a role for this growth factor in tumo rigenesis. METHODS. Using immunohistochemistry, the expression, preval ence, and distribution of TGF-beta isoforms were evaluated in 25 high grade human osteosarcomas. The Cox proportional hazards models and Kap lan-Meier curves were calculated correlating disease free survival wit h TGF-beta expression. RESULTS. Expression of one or more TGF-beta iso forms was found in all the osteosarcomas. Immunoreactivity for TGF-bet a 1 and TGF-beta 3 generally was stronger than for TGF-beta 2. The cyt oplasm of the tumor cells showed stronger staining than their surround ing extracellular stroma. Most notably, osteoclasts showed strong to i ntense staining for all three isoforms. In 11 of 25 specimens angiogen ic activity was noted with staining of multiple small vessels in the t umor stroma. Expression of TGF-beta 3, but not of TGF-beta 2 or TGF-be ta 1, related to disease progression, such that there was a statistica lly significant decrease in the disease free interval as the immunorea ctivity for TGF-beta 3 increased. CONCLUSIONS. All osteosarcomas expre ssed TGF-beta in the cytoplasm of the tumor cells as well as in their extracellular stroma. The presence of TGF-beta in the endothelial and perivascular layers of small vessels in the tumor stroma suggests angi ogenic activity of this growth factor. The expression of TGF-beta 3 wa s correlated strongly with disease progression (P = 0.027). These data suggest that increased expression of TGF-beta isoforms, especially TG F-beta 3, may play a role in osteosarcoma progression. (C) 1997 Americ an Cancer Society.