Open Access Highly Accessed Research article

Smad4-expression is decreased in breast cancer tissues: a retrospective study

Christina H Stuelten124*, Miriam B Buck2, Juergen Dippon3, Anita B Roberts4, Peter Fritz1 and Cornelius Knabbe1

Author Affiliations

1 Department of Clinical Chemistry, Robert Bosch Hospital, Stuttgart, Germany

2 Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany

3 University of Stuttgart, Department of Mathematics, Stuttgart, Germany

4 NIH, NCI, Laboratory of Cell Regulation and Carcinogenesis, Bethesda, MD, USA

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BMC Cancer 2006, 6:25  doi:10.1186/1471-2407-6-25

Published: 26 January 2006



Although transforming growth factor β (TGF-β) typically inhibits proliferation of epithelial cells, consistent with a tumor suppressor activity, it paradoxically also exhibits pro-metastatic activity in the later stages of carcinogenesis. Since tumors often display altered TGF-β signaling, particularly involving the Smad-pathway, we investigated the role of Smad4-expression in breast cancer.


Smad4 expression was investigated by immunohistochemistry in formalin-fixed, paraffin-embedded tissue from 197 samples of primary breast cancer obtained between 1986 and 1998. The prognostic value of Smad4-expression was analyzed.


Smad4 expression was found to be reduced in lobular and ductal breast carcinoma as compared to surrounding uninvolved lobular and ductal breast epithelia (p < 0.001, n = 50). Smad4-expression correlated positively with expression of TGF-β-receptor I (p < 0.001, n = 197) and TGF-β-receptor II (p < 0.001, n = 197), but showed no significant correlation with tumor size, metastases, nodal status, histological grade, histological type, or estrogen receptor expression. While not achieving statistical significance, there was a trend towards longer survival times in patients with Smad4 negative tumors.


According to the suggested role of Smad4 as a tumor suppressor we observed that expression of Smad4 is lower in human breast cancer than in surrounding breast epithelium. However, we also observed a trend towards longer survival times in Smad4-negative patients, indicating the complex role of TGF-β signaling in tumor progression.