title: Histomolecular phenotypes and outcome in adenocarcinoma of the ampulla of vater.
abstract: OBJECTIVE
  Individuals with adenocarcinoma of the ampulla of Vater demonstrate a broad range of outcomes, presumably because these cancers may arise from any one of the three epithelia that converge at that location. This variability poses challenges for clinical decision making and the development of novel therapeutic strategies.
  
  
  METHODS
  We assessed the potential clinical utility of histomolecular phenotypes defined using a combination of histopathology and protein expression (CDX2 and MUC1) in 208 patients from three independent cohorts who underwent surgical resection for adenocarcinoma of the ampulla of Vater.
  
  
  RESULTS
  Histologic subtype and CDX2 and MUC1 expression were significant prognostic variables. Patients with a histomolecular pancreaticobiliary phenotype (CDX2 negative, MUC1 positive) segregated into a poor prognostic group in the training (hazard ratio [HR], 3.34; 95% CI, 1.69 to 6.62; P < .001) and both validation cohorts (HR, 5.65; 95% CI, 2.77 to 11.5; P < .001 and HR, 2.78; 95% CI, 1.25 to 7.17; P = .0119) compared with histomolecular nonpancreaticobiliary carcinomas. Further stratification by lymph node (LN) status defined three clinically relevant subgroups: one, patients with histomolecular nonpancreaticobiliary (intestinal) carcinoma without LN metastases who had an excellent prognosis; two, those with histomolecular pancreaticobiliary carcinoma with LN metastases who had a poor outcome; and three, the remainder of patients (nonpancreaticobiliary, LN positive or pancreaticobiliary, LN negative) who had an intermediate outcome.
  
  
  CONCLUSIONS
  Histopathologic and molecular criteria combine to define clinically relevant histomolecular phenotypes of adenocarcinoma of the ampulla of Vater and potentially represent distinct diseases with significant implications for current therapeutic strategies, the ability to interpret past clinical trials, and future trial design.
authors: Cancer Research Program, Garvan Institute of Medical Research, Sydney, NSW 2010 Australia.
authors: David K
authors: DK
authors: Chang
authors: Nigel B
authors: NB
authors: Jamieson
authors: Amber L
authors: AL
authors: Johns
authors: Christopher J
authors: CJ
authors: Scarlett
authors: Marina
authors: M
authors: Pajic
authors: Angela
authors: A
authors: Chou
authors: Mark
authors: M
authors: Pinese
authors: Jeremy L
authors: JL
authors: Humphris
authors: Marc D
authors: MD
authors: Jones
authors: Christopher
authors: C
authors: Toon
authors: Adnan M
authors: AM
authors: Nagrial
authors: Lorraine A
authors: LA
authors: Chantrill
authors: Venessa T
authors: VT
authors: Chin
authors: Andreia V
authors: AV
authors: Pinho
authors: Ilse
authors: I
authors: Rooman
authors: Mark J
authors: MJ
authors: Cowley
authors: Jianmin
authors: J
authors: Wu
authors: R Scott
authors: RS
authors: Mead
authors: Emily K
authors: EK
authors: Colvin
authors: Jaswinder S
authors: JS
authors: Samra
authors: Vincenzo
authors: V
authors: Corbo
authors: Claudio
authors: C
authors: Bassi
authors: Massimo
authors: M
authors: Falconi
authors: Rita T
authors: RT
authors: Lawlor
authors: Stefano
authors: S
authors: Crippa
authors: Nicola
authors: N
authors: Sperandio
authors: Samantha
authors: S
authors: Bersani
authors: Euan J
authors: EJ
authors: Dickson
authors: Mohamed A A
authors: MA
authors: Mohamed
authors: Karin A
authors: KA
authors: Oien
authors: Alan K
authors: AK
authors: Foulis
authors: Elizabeth A
authors: EA
authors: Musgrove
authors: Robert L
authors: RL
authors: Sutherland
authors: James G
authors: JG
authors: Kench
authors: C Ross
authors: CR
authors: Carter
authors: Anthony J
authors: AJ
authors: Gill
authors: Aldo
authors: A
authors: Scarpa
authors: Colin J
authors: CJ
authors: McKay
authors: Andrew V
authors: AV
authors: Biankin
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater / Q000378:metabolism* / Q000473:pathology; D000071616:CDX2 Transcription Factor; D015331:Cohort Studies; D003138:Common Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D053554:Keratin-20 / Q000096:biosynthesis; D053552:Keratin-7 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000096:biosynthesis*; D055262:Mucin-2 / Q000096:biosynthesis; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D053554:Keratin-20; D053552:Keratin-7; C060192:MUC1 protein, human; C524625:MUC2 protein, human; D018396:Mucin-1; D055262:Mucin-2