Expression pattern of p-Smad2/Smad4 as a predictor of survival in invasive breast ductal carcinoma

The present study examined SMAD family member 4 (Smad4), SMAD family member 2 (Smad2) and phosphorylated (p-)Smad2 expression in biopsy specimens from patients with invasive breast ductal carcinoma, in order to assess their abilities as prognostic markers. A total of 126 tissue samples were selected, and the expression of Smad2, p-Smad2 and Smad4 in carcinoma tissues was detected by immunostaining, and the association between protein expression and clinicopathological variables was analyzed. Smad4 expression was negatively correlated with human epidermal growth factor receptor 2 in carcinoma tissues, and Smad4 expression was consistent with that of p-Smad2. Although multivariate analysis revealed that Smad2, p-Smad2 and Smad4 were not independent predictors, Kaplan-Meier curves demonstrated that Smad4 positivity was correlated with a longer overall survival (OS) and progression-free survival (PFS) time. However, upon analysis of combined markers, there was a significant difference between the p-Smad2/Smad4 co-positive and co-negative patients; the latter tended to exhibit a shorter OS and PFS time, and multivariate analysis revealed that the combined expression of p-Smad2 and Smad4 may be used as an independent prognostic factor. These results suggested that the assessment of p-Smad2 and Smad4 protein expression in breast ductal carcinoma biopsy specimens may provide additional prognostic information.