title: Histomorphologic and molecular phenotypes predict gemcitabine response and overall survival in adenocarcinoma of the ampulla of Vater.
abstract: BACKGROUND
  The need for adjuvant chemotherapy after resection of ampullary cancer (PapCa) remains undefined. Recent data suggest that a different epithelial origin of PapCa might be associated with different tumor biology. The aim of the present study was to assess the clinical value of morphologic and immunohistochemic subclassification of PapCa into intestinal-type (IT) and pancreaticobiliary-type (PT) to predict chemotherapy response and overall survival (OS).
  
  
  METHODS
  Via a prospective database, 112 PapCa were identified, of which 95 could be included in the present study. Those were compared with 206 matching patients with periampullary pancreatic cancer (ie, pancreatic ductal adenocarcinoma, PDAC). IT and PT PapCa were classified morphologically, and tissue microarray was prepared with immunohistochemistry for CK7, CK20, MUC2, CDX2, ß-Catenin, and Villin. Multivariate survival analysis was performed.
  
  
  RESULTS
  OS of PT patients was less compared with IT patients (25 vs 98 months; P < .001), whereas it was comparable with patients with PDAC (25 vs 14 months; P = .123). PT patients receiving adjuvant gemcitabine chemotherapy featured improved OS (32 vs 13 months; P = .013), whereas gemcitabine tended to be associated with decreased OS in IT patients (35 vs 112 months; P = .193). Besides histopathologic classification, expression of CK7 and MUC2 were important prognostic variables. PT patients with CK7-positivity or MUC2-negativity were segregated into an even poorer prognostic group.
  
  
  CONCLUSIONS
  PapCa is not a separate tumor entity. We demonstrate important differences between IT-PapCa and PT-PapCa not only in long-term survival but also in response to adjuvant gemcitabine. Tumor biology and clinical course of PT tumors resemble those of PDAC. PT tumors should therefore be treated like PDAC.
authors.affiliation: Department of General-, Visceral-, Transplantation-, Vascular- and Thoracic Surgery, University of Munich, Munich, Germany; Pancreatic Cancer Center Munich(LMU), University of Munich, Munich, Germany.
authors.forename: Tobias S
authors.initials: TS
authors.lastname: Schiergens
authors.affiliation: Pancreatic Cancer Center Munich(LMU), University of Munich, Munich, Germany; Department of Pathology, University of Munich, Munich, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Reu
authors.affiliation: Pancreatic Cancer Center Munich(LMU), University of Munich, Munich, Germany; Department of Pathology, University of Munich, Munich, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Neumann
authors.affiliation: Pancreatic Cancer Center Munich(LMU), University of Munich, Munich, Germany; Division of Digestive and Liver Diseases, Irving Cancer Research Center, Columbia University Medical Center, New York, NY.
authors.forename: Bernhard W
authors.initials: BW
authors.lastname: Renz
authors.affiliation: Department of General-, Visceral-, Transplantation-, Vascular- and Thoracic Surgery, University of Munich, Munich, Germany; Pancreatic Cancer Center Munich(LMU), University of Munich, Munich, Germany.
authors.forename: Hanno
authors.initials: H
authors.lastname: Niess
authors.affiliation: Pancreatic Cancer Center Munich(LMU), University of Munich, Munich, Germany; Department of Medical Oncology, University of Munich, Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Boeck
authors.affiliation: Pancreatic Cancer Center Munich(LMU), University of Munich, Munich, Germany; Department of Medical Oncology, University of Munich, Munich, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
authors.affiliation: Department of General-, Visceral- and Vascular Surgery, University of Magdeburg, Magdeburg, Germany.
authors.forename: Christiane J
authors.initials: CJ
authors.lastname: Bruns
authors.affiliation: Department of General-, Visceral-, Transplantation-, Vascular- and Thoracic Surgery, University of Munich, Munich, Germany; Pancreatic Cancer Center Munich(LMU), University of Munich, Munich, Germany.
authors.forename: Karl-Walter
authors.initials: KW
authors.lastname: Jauch
authors.affiliation: Department of General-, Visceral-, Transplantation-, Vascular- and Thoracic Surgery, University of Munich, Munich, Germany; Pancreatic Cancer Center Munich(LMU), University of Munich, Munich, Germany. Electronic address: axel.kleespies@med.lmu.de.
authors.forename: Axel
authors.initials: A
authors.lastname: Kleespies
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater / Q000473:pathology* / Q000502:physiology; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D003138:Common Bile Duct Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D016208:Databases, Factual; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016019:Survival Analysis; D046888:Tissue Array Analysis; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine