J Breast Dis.  2019 Dec;7(2):52-58. 10.14449/jbd.2019.7.2.52.

Clinicopathological Significance of SMAD4 Expression in Breast Cancer

  • 1Department of Surgery, College of Medicine, Hanyang University, Seoul, Korea. bovie@hanyang.ac.kr
  • 2Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea.


SMAD4 is a member of the SMAD family and acts as a central mediator of transforming growth factor beta signaling. Little is known about SMAD4 expression and its prognostic significance in breast cancer. We evaluated the clinicopathological and prognostic significance of SMAD4 expression in breast cancer.
Two hundred and fifty-five patients with invasive ductal carcinoma of the breast from 2000 to 2008 were retrospectively analyzed. We investigated SMAD4 expression using a tissue microarray-based immunohistochemical assay and evaluated the association between SMAD4 and prognosis of breast cancer.
High SMAD4 expression was positively associated with early stage (p=0.009), estrogen receptor positivity (p=0.026), and human epidermal growth factor receptor 2 negativity (p=0.001). A significant difference in overall survival (OS) was associated with high SMAD4 expression in patients with T1 stage tumors (hazard ratio: 0.459, p=0.024).
High SMAD4 expression was correlated with several favorable prognostic factors and was associated with favorable OS in T1 stage breast cancer. SMAD4 in breast cancer has potential prognostic significance, and further investigations and understanding about SMAD4 expression are needed.


Breast neoplasms; Prognosis; SMAD4 protein; Transforming growth factor beta
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