Prognostic significance of TGF beta 1 and TGF beta 3 in human breast carcinoma

Abstract

Transforming growth factor beta s (TGF beta s) are multifunctional growth factors which show differential expression both temporally and spatially and exert pleiotropic effects during carcinogenesis. Although all three mammalian isoforms of TGF beta share considerable sequence similarity, they appear to have distinct functions in health and disease, such as embryogenesis, wound healing and tumourigenesis. Much of our knowledge about the relationship between TGF beta s and breast cancer is based on publications on TGF beta 1 but the role of TGF beta 3 in the progression of breast cancer has not been well documented. In the present study, the expression of TGF beta 1 and TGF beta 3 was assessed by immunohistochemistry. Of the 153 invasive breast cancer tissues, TGF beta 1 was expressed strongly in 25 and moderately in 98 cases. The immunoreactivity of TGF beta 3 was comparable with TGF beta 1, which was expressed strongly in 21 and moderately in 104 cases. The two isoforms were coexpressed in 111 (72.5%) tumours and were absent in 16 cases (10%). Immunostaining for TGFb3 but not TGF beta 1 was inversely correlated with overall survival (p = 0.0204). When combined with lymph node involvement, TGFb3 became an even more significant prognostic factor for overall survival (p = 0.0003), i.e. patients with node metastasis and positive TGFb3 expression had a worse prognosis: the risk of death for these patients was thirteen-fold greater than those who had no node involvement. The fact that it has been reported previously that high TGF beta 3 plasma levels in patients with untreated early stage breast cancer were correlated with subsequent lymph node metastasis and it was observed in the present study too, that TGF beta 3 expression in breast tumours was an independent predictor of overall survival, led us to suggest that the simultaneous measurement of TGF beta 3 in plasma and its expression in resected tumour tissues in the same cohort of patients may prove to be an important parameter in assessing tumour progression.