Lack of activated Smad2 in transforming growth factor-β signaling is an unfavorable prognostic factor in patients with esophageal squamous cell carcinoma

Background and Objectives: Transforming growth factor-beta (TGF-beta) regulates cell growth in various cells, and inactivation of the TGF-beta-signaling pathway contributes to tumor progression. In this study, we investigated the expression of Smad2 and Smad3, which are specific intracellular mediators of TGF-beta signaling. We also examined the relationship between the expression levels of activated Smad2 by TGF-beta and clinicopathologic characteristics of patients with esophageal squamous cell carcinoma (SCC). Methods: Immunohistochemical staining with anti-phosphorylated Smad2 (P-Smad2) polyclonal antibody, anti-Smad2 monoclonal antibody, and anti-Smad3 polyclonal antibody was performed on surgical specimens obtained from 80 patients with esophageal SCC. Results: Our data indicated that a low level of P-Smad2, as detected immunohistologically, correlated with lymph node metastasis (P=0.0002), distant metastasis (P = 0.0338), pathologic stage (P = 0.0093), and poor survival rate (P = 0.0246). All patients without positive Smad2 immunostaining were included among those without positive P-Smad2 immunostaining. There was no significant correlation between expression of Smad2 or Smad3 and clinicopathologic characteristics. Conclusions: We demonstrated that a lack of Smad2-P appears to be correlated with tumor development and poor prognosis in patients with esophageal SCC.