title: Detailed analysis of epithelial-mesenchymal transition and tumor budding identifies predictors of long-term survival in pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive biology and poor prognosis even after resection. Long-term survival is very rare and cannot be reliably predicted. Experimental data suggest an important role of epithelial-mesenchymal transition (EMT) in invasion and metastasis of PDAC. Tumor budding is regarded as the morphological correlate of local invasion and cancer cell dissemination. The aim of this study was to evaluate the biological and prognostic implications of EMT and tumor budding in PDAC of the pancreatic head.
  
  
  METHODS
  Patients were identified from a prospectively maintained database, and baseline, operative, histopathological, and follow-up data were extracted. Serial tissue slices stained for Pan-Cytokeratin served for analysis of tumor budding, and E-Cadherin, Beta-Catenin, and Vimentin staining for analysis of EMT. Baseline, operative, standard pathology, and immunohistochemical parameters were evaluated for prediction of long-term survival (≥ 30 months) in uni- and multivariate analysis.
  
  
  RESULTS
  Intra- and intertumoral patterns of EMT marker expression and tumor budding provide evidence of partial EMT induction at the tumor-host interface. Lymph node ratio and E-Cadherin expression in tumor buds were independent predictors of long-term survival in multivariate analysis.
  
  
  CONCLUSIONS
  Detailed immunohistochemical assessment confirms a relationship between EMT and tumor budding at the tumor-host interface. A small group of patients with favorable prognosis can be identified by combined assessment of lymph node ratio and EMT in tumor buds.
authors.affiliation: Institute of Pathology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Ilona
authors.initials: I
authors.lastname: Kohler
authors.forename: Peter
authors.initials: P
authors.lastname: Bronsert
authors.forename: Sylvia
authors.initials: S
authors.lastname: Timme
authors.forename: Martin
authors.initials: M
authors.lastname: Werner
authors.forename: Thomas
authors.initials: T
authors.lastname: Brabletz
authors.forename: Ulrich Theodor
authors.initials: UT
authors.lastname: Hopt
authors.forename: Oliver
authors.initials: O
authors.lastname: Schilling
authors.forename: Dirk
authors.initials: D
authors.lastname: Bausch
authors.forename: Tobias
authors.initials: T
authors.lastname: Keck
authors.forename: Ulrich Friedrich
authors.initials: UF
authors.lastname: Wellner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015820:Cadherins / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005544:Forecasting; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D013997:Time Factors
chemical_list: D015820:Cadherins
keywords: E-Cadherin; epithelial-mesenchymal transition; pancreatic cancer; pancreatic ductal adenocarcinoma; pancreatoduodenectomy; tumor budding