BACKGROUND: Recent investigations have demonstrated the clinical significance of intralesional mean vessel density (ILVD), as a marker of tumor angiogenesis.The role of growth factors in mediating angiogenesis has also been well documented. Transforming growth factor beta (TGFbeta) belongs to a family of polypeptideswith diverse biological functions. Very few studies however have looked at the role of this growth factor in relation to angiogenesis. This study analyzed the significance of TGF beta in relation to CD34, an endothelial cell marker, the extent of apoptosis, and tissue proliferation defined by Ki67 expression in breast cancer. METHODS: The extent of apoptosis was defined by morphological criteria and the Tdt-mediated dUTP biotin nick end labelling (TUNEL) assay. Immunocytochemistry was performed to measure TGF beta, CD34 and Ki67 expression. RESULTS: An inverse association was observed between TGF beta expression and ILVD as evident by CD34 labelling (r= -0.31182, p= 0.00005). TGF beta expression didnot correlate with either TUNEL reactivity or Ki67 expression. CD34 and TGF beta expression also had no relationship with histopathologi-cal grade. No correlation was observed between CD34 expression and apoptosis. However a statistically significant correlation was observed between CD34 and Ki67 expression. CONCLUSION: These results suggest that breast cancer cells synthesize TGF beta that, through paracrine mechanisms, may inhibit proliferation of vascular endothelium rather than their own growth. Moreover the data also suggest that decreased expression of TGF beta was associated with an increase in neovascularization, whichin turn would increase the tumor proliferative fraction.
BACKGROUND: Recent investigations have demonstrated the clinical significance of intralesional mean vessel density (ILVD), as a marker of tumor angiogenesis.The role of growth factors in mediating angiogenesis has also been well documented. Transforming growth factor beta (TGFbeta) belongs to a family of polypeptideswith diverse biological functions. Very few studies however have looked at the role of this growth factor in relation to angiogenesis. This study analyzed the significance of TGF beta in relation to CD34, an endothelial cell marker, the extent of apoptosis, and tissue proliferation defined by Ki67 expression in breast cancer. METHODS: The extent of apoptosis was defined by morphological criteria and the Tdt-mediated dUTP biotin nick end labelling (TUNEL) assay. Immunocytochemistry was performed to measure TGF beta, CD34 and Ki67 expression. RESULTS: An inverse association was observed between TGF beta expression and ILVD as evident by CD34 labelling (r= -0.31182, p= 0.00005). TGF beta expression didnot correlate with either TUNEL reactivity or Ki67 expression. CD34 and TGF beta expression also had no relationship with histopathologi-cal grade. No correlation was observed between CD34 expression and apoptosis. However a statistically significant correlation was observed between CD34 and Ki67 expression. CONCLUSION: These results suggest that breast cancer cells synthesize TGF beta that, through paracrine mechanisms, may inhibit proliferation of vascular endothelium rather than their own growth. Moreover the data also suggest that decreased expression of TGF beta was associated with an increase in neovascularization, whichin turn would increase the tumor proliferative fraction.
Authors: H Funahashi; T Imai; Y Tanaka; K Tsukamura; Y Hayakawa; T Kikumori; T Mase; T Itoh; M Nishikawa; H Hayashi; A Shibata; Y Hibi; M Takahashi; T Narita Journal: Jpn J Cancer Res Date: 1999-09