title: Validation of histomolecular classification utilizing histological subtype, MUC1, and CDX2 for prognostication of resected ampullary adenocarcinoma.
abstract: BACKGROUND
  Outcomes for ampullary adenocarcinomas are heterogeneous, and numerous methods of categorisation exist. A histomolecular phenotype based on histology, caudal-type homeodomain transcription factor 2 (CDX2) staining and Mucin 1 (MUC1) staining has recently been tested and validated in two cohorts. We attempt to validate this classification in a large patient population.
  
  
  METHODS
  Tissue samples from 163 patients with resected ampullary adenocarcinoma were classified based on histology and immunohistochemical expression of CDX2 and MUC1. A pancreaticobiliary histomolecular classification (PB) was defined as a sample with pancreaticobiliary histology, positive MUC1 and negative CDX2 expression.
  
  
  RESULTS
  There were 82 deaths; median follow-up of 32.4 months; and median overall survival of 87.7 (95% CI 42.9-109.5) months. PB comprised 28.2% of the cases. Factors associated with overall survival were histological subtype (P=0.0340); T1/2 vs T3/4 (P=0.001); perineural (P<0.0001) and lymphovascular (P=0.0203) invasion; and histomolecular intestinal histomolecular phenotype (INT) vs PB phenotype (106.4 vs 21.2 months, P<0.0001). Neither MUC1 nor CDX2 was statistically significant, although MUC1 positivity defined as ⩾10% staining was significant (P=0.0023). In multivariate analysis, age (HR 1.03), PB phenotype (HR 2.26) and perineural invasion (PNI; HR 2.26) were associated with poor survival.
  
  
  CONCLUSIONS
  The prognostic ability of histomolecular phenotype has been validated in an independent cohort of ampullary adenocarcinoma patients.
authors.affiliation: Division of Cancer Medicine, Department of Graduate Medical Education, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: A
authors.initials: A
authors.lastname: Schueneman
authors.affiliation: 1] Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA [2] Department of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA [3] Department of Oncology, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Goggins
authors.affiliation: Department of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ensor
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Saka
authors.affiliation: Division of Pathology/Lab Medicine, Department of Pathology, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: N
authors.initials: N
authors.lastname: Neishaboori
authors.affiliation: Division of Pathology/Lab Medicine, Department of Pathology, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.affiliation: Division of Pathology/Lab Medicine, Department of Pathology, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: A
authors.initials: A
authors.lastname: Maitra
authors.affiliation: Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: G
authors.initials: G
authors.lastname: Varadhachary
authors.affiliation: Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: N
authors.initials: N
authors.lastname: Rezaee
authors.affiliation: Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: C
authors.initials: C
authors.lastname: Wolfgang
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: V
authors.initials: V
authors.lastname: Adsay
authors.affiliation: Division of Pathology/Lab Medicine, Department of Pathology, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Overman
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater / Q000473:pathology*; D000071616:CDX2 Transcription Factor; D015331:Cohort Studies; D003138:Common Bile Duct Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism*; D011379:Prognosis
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; C060192:MUC1 protein, human; D018396:Mucin-1