Expression Pattern of Smad4/GATA3 as a Predictor of Survival in Invasive Ductal Carcinoma of the Breast

Pathobiology. 2017;84(3):130-138. doi: 10.1159/000449428. Epub 2017 Mar 14.

Abstract

Background: Smad4 and GATA3 proteins are known prognostic markers in various cancers. Smad4 is a mediator linked to both tumour suppression and progression. GATA3 is a regulator of development and morphogenesis of the mammary gland. We assessed and compared the predictive performance of Smad4 and GATA3 for clinical outcomes in patients with breast cancer.

Methods: The combined expression pattern based on Smad4+/- and GATA3+/- was evaluated by immunostaining using breast cancer tissue microarray, and the relationships between protein expression and clinicopathological variables were analysed.

Results: Smad4 expression was only associated with an ill-defined tumour border, whereas GATA3 was associated with several good prognostic factors. On analysis of combined markers, there was a significant difference in the expression of fascin (an important factor for cancer invasiveness) between the Smad4+/GATA3- and Smad4-/GATA3+ groups. Smad4+/GATA3- was correlated with worse clinicopathological parameters, relapse-free survival (RFS), and overall survival (OS), compared to Smad4-/GATA3+.

Conclusion: Combined markers of Smad4/GATA3 showed a superior performance compared to single markers for predicting RFS and OS in patients with breast cancer.

Keywords: Breast cancer; GATA3 protein; Prognosis; Smad4 protein.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / pathology
  • Disease-Free Survival
  • Female
  • GATA3 Transcription Factor / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Middle Aged
  • Prognosis
  • Smad4 Protein / metabolism*
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • SMAD4 protein, human
  • Smad4 Protein