Transforming growth factor beta related to extent of tumor angiogenesis but not apoptosis or proliferation in breast carcinoma

Abstract

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 (TGF/β) belongs to a family of polypeptides with 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 TGFβ 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. Immunocyfochemistry was performed to measure TGFβ, CD34 and Ki67 expression. Results An inverse association was observed between TGFβ expression and ILVD as evident by CD34 labelling (r=-0.31182, p=0.00005). TGFβ expression did not correlate with either TUNEL reactivity or Ki67 expression. CD34 and TGFβ expression also had no relationship with histopathological grade. No correlation was observed between CD34 expression and apoptosis. However a statistically significant correlation was observed between CD34 and Ki67 expression. Conclusions: These results suggest that breast cancer cells synthesize TGFβ that, through paracrine mechanisms, may inhibit proliferation of vascular endothelium rather than their own growth Moreover the data also suggest that decreased expression of TGFβ was associated with on increase in neovascularization, which in turn would increase the tumor proliferative fraction.