title: SMAD4 expression predicts local spread and treatment failure in resected pancreatic cancer.
abstract: 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.
authors.affiliation: From the *Departments of Gastroenterological Surgery (Surgery II) and †Pathology, Graduate School of Medicine, Nagoya University Hospital, Nagoya University; and ‡Department of Surgery, Nagoya Central Hospital, Nagoya, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Yamada
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujii
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Shimoyama
authors.forename: Mitsuro
authors.initials: M
authors.lastname: Kanda
authors.forename: Goro
authors.initials: G
authors.lastname: Nakayama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugimoto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koike
authors.forename: Shuji
authors.initials: S
authors.lastname: Nomoto
authors.forename: Michitaka
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Akimasa
authors.initials: A
authors.lastname: Nakao
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodera
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016577:Pancreaticoduodenectomy; D011379:Prognosis; D051901:Smad4 Protein / Q000378:metabolism*; D017211:Treatment Failure
chemical_list: D014408:Biomarkers, Tumor; C497796:SMAD4 protein, human; D051901:Smad4 Protein