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

BACKGROUND: The transforming growth factor beta (TGFbeta) 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 TGFbeta-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 T12,N0 breast cancer were examined. The expression of TGFbeta-1, pSmad2 and Smad4 was assessed implementing immunohistochemical assays.

RESULTS: TGFbeta-I, 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 TGFbeta-1 were 4.6 times more likely to experience distant recurrence.

CONCLUSION: Our results demonstrate that pSmad2/3 and TGFP-1 may be promising novel prognostic markers for T1.2,N0 breast carcinomas.