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

Transforming growth factor betas (TGF betas) are multifunctional growth fac tors which show differential expression both temporally and spatially and e xert pleiotropic effects during carcinogenesis. Although all three mammalia n isoforms of TGF beta share considerable sequence similarity, they appear to have distinct functions in health and disease, such as embryogenesis, wo und healing and tumourigenesis. Much of our knowledge about the relationshi p between TGF betas and breast cancer is based on publications on TGF beta1 but the role of TGF beta3 in the progression of breast cancer has not been well documented. In the present study, the expression of TGF beta1 and TGF beta3 was assessed by immunohistochemistry. Of the 153 invasive breast can cer tissues, TGF beta1 was expressed strongly in 25 and moderately in 98 ca ses. The immunoreactivity of TGF beta3 was comparable with TGF beta1, 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 beta1 was inversely correlated with o verall survival (p=0.0204). When combined with lymph node involvement, TGFb 3 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-fo ld greater than those who had no node involvement. The fact that it has bee n reported previously that high TGF beta3 plasma levels in patients with un treated early stage breast cancer were correlated with subsequent lymph nod e metastasis and it was observed in the present study too, that TGF beta3 e xpression in breast tumours was an independent predictor of overall surviva l, led us to suggest that the simultaneous measurement of TGF beta3 in plas ma and its expression in resected tumour tissues in the same cohort of pati ents may prove to be an important parameter in assessing tumour progression .