Prognostic Significance of TGF beta -1 and pSmad2/3 in Breast Cancer Patients with T sub(1-2),N sub(0) Tumours

Background: The transforming growth factor beta (TGF beta ) 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 T sub(1-2),N sub(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 T sub(1-2),N sub(0) breast carcinomas.