SMAD4 Expression Predicts Local Spread and Treatment Failure in Resected Pancreatic Cancer

OBJECTIVE The purpose of this study was to evaluate the prognostic relevance of SMAD4 expression in pancreatic cancer. METHODS We analyzed the correlations between SMAD4 expression and clinicopathological parameters and outcome in 174 patients with pancreatic cancer. Specimens were also classified into subtypes reflecting epithelial-to-mesenchymal transition, based on E-cadherin and vimentin. RESULTS We found that 59.8% (104/174) of patients were SMAD4 and 40.2% (70/174) were SMAD4. Disease-specific survival in patients with SMAD4 was significantly better than that in SMAD4. SMAD4 status was significantly correlated with portal vein invasion, lymph vessel invasion, and perineural invasion and was an independent prognostic factor. SMAD4 was significantly associated with mesenchymal phenotype. The loss of SMAD4 expression was found in 49.4% of patients with no vascular invasion, 61.9% with portal vein invasion, 76.5% with common hepatic artery invasion, and 80.8% with superior mesenteric artery invasion. In addition, the specimens from 59.0% of patients with local recurrence, 66.7% of those with both local and distant recurrence, and 73.7% of those with distant recurrence were SMAD4. CONCLUSIONS The loss of SMAD4 expression is an independent prognostic factor and seems to be associated with tumor progression, pattern of failure, and epithelial-to-mesenchymal transition status. Preoperative stratification based on SMAD4 could lead to appropriate treatment strategy.