title: Phenotypic characterization and clinical outcome in ampullary adenocarcinoma.
abstract: BACKGROUND
  Although various features of ampullary adenocarcinoma have been reported, the impact of genetic alterations and rare subtypes on clinical outcome remains unclear.
  
  
  METHODS
  We determined the expression of proteins, including MUC1, MUC2, p53, p16, Smad/Dpc4, and β-catenin, and genetic mutations such as KRAS, BRAF, and GNAS mutations in 69 patients with ampullary adenocarcinoma to clarify their relationships with clinicopathological findings and subtypes.
  
  
  RESULTS
  Kaplan-Meier survival analysis indicated that abnormal p53 labeling was significantly associated with a shorter overall survival. MUC1-positive and MUC2-negative expressions were significantly associated with lymphatic invasion, pancreatic invasion, lymph node metastasis, and advanced UICC stage. The KRAS mutation was significantly associated with large tumor size and pancreatic invasion. There were 35 intestinal (50%), 15 pancreatobiliary (22%), and 11 mixed subtype (16%) tumors. Patients with the mixed subtype showed significantly poor outcome. The invasiveness of the mixed subtype was similar to that of the pancreatobiliary subtype; moreover, the mixed subtype showed a high incidence of abnormal β-catenin immunolabeling (73%).
  
  
  CONCLUSIONS
  Protein expression and genetic mutation are clinically associated with the characteristics of ampullary adenocarcinoma. The mixed subtype may have a distinct tumor nature as compared to other two major subtypes. J. Surg. Oncol. 2016;114:119-127. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Gastroenterological Surgery, Kagawa University, Kagawa, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Asano
authors.affiliation: Department of Gastroenterological Surgery, Kagawa University, Kagawa, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Okano
authors.affiliation: Department of Gastroenterological Surgery, Kagawa University, Kagawa, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Oshima
authors.affiliation: Department of Pathology, Kagawa University, Kagawa, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Kagawa
authors.affiliation: Department of Pathology, Kagawa University, Kagawa, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kushida
authors.affiliation: Department of First Surgery, Kochi University School of Medicine, Kochi, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Munekage
authors.affiliation: Department of First Surgery, Kochi University School of Medicine, Kochi, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hanazaki
authors.affiliation: Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Jota
authors.initials: J
authors.lastname: Watanabe
authors.affiliation: Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Yasutsugu
authors.initials: Y
authors.lastname: Takada
authors.affiliation: Department of Digestive and Transplant Surgery, Tokushima University, Tokushima, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ikemoto
authors.affiliation: Department of Digestive and Transplant Surgery, Tokushima University, Tokushima, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
authors.affiliation: Department of Gastroenterological Surgery, Kagawa University, Kagawa, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D003138:Common Bile Duct Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers
keywords: ampullary adenocarcinoma; mixed type; p53; pathologic subtype; β-catenin