Prognostic significance of TGFβ-1 and pSmad2/3 in breast cancer patients with T1-2,N0 tumours

Background: The transforming growth factor beta (TGF) signaling pathway has been shown to exert divergent effects and to cross-talk with estrogen pathways in mammary gland tumorigenesis. TGF signaling in early stage breast cancer was investigated by examining the expression of TGF beta-1 and the signaling mediators pSmad2/3 and Smad4. Their association with oestrogen and progesterone receptors, as well as with clinical and pathological features was also analyzed. Patients and Methods: Sixty-one tumor specimens from surgically treated patients with primary T1-2,N-0 breast cancer were examined. The expression of TGF beta-1, pSmad2 and Smad4 was assessed implementing immunohistochemical assays. Results: TGF beta-1, pSmad2/3 and Smad4 were expressed in 50.9%, 74.0% and 61.0% of specimens, respectively. The degree of expression of the three molecules was significantly associated with each other. Loss of pSmad2/3 expression indicated a shorter disease-free survival in all patients, including those with oestrogen receptor-positive tumors. Patients not expressing TGF beta-1 were 4.6 times more likely to experience distant recurrence. Conclusion: Our results demonstrate that pSmad2/3 and TGF beta-1 may be promising novel prognostic markers for T1-2,N-0 breast carcinomas.