title: Performance and prognostic utility of the 92-gene assay in the molecular subclassification of ampullary adenocarcinoma.
abstract: Ampullary adenocarcinoma is a rare gastrointestinal cancer associated with diverse outcomes due to clinical and pathological heterogeneity. Standardized methods to better prognosticate and inform therapeutic selection for ampullary adenocarcinoma are needed. This study explored the novel use and potential prognostic utility of a 92-gene cancer classifier in ampullary adenocarcinomas.
  
  
  
  In this prospectively-defined, blinded study of ampullary adenocarcinoma [N =54; stage T3 or higher (57 %); Grade III (44 %); Node positive (55 %)], the performance of a 92-gene classifier was examined to predict the ampullary subtype that was derived from histomorphological examination of resected ampullary samples. Outcome data for relapse-free survival (RFS) and overall survival (OS) were plotted to compare the prognostic utility of histological subtyping, histomolecular phenotyping, and the 92-gene classifier. Multivariate analysis was used to determine clinicopathological variables that were independently associated with overall survival.
  
  
  
  The 92-gene classifier demonstrated sensitivities and specificities of 85 % [95 % CI, 66-94] and 68 % [95 % CI, 48-84] and 64 % [95 % CI, 46-79] and 88 % [95 % CI, 70-98] for the pancreaticobiliary and intestinal histological subtypes, respectively. For the 92-gene classifier, improved outcomes were observed for the intestine versus the pancreaticobiliary prediction (median OS 108.1 v 36.4 months; HR, 2.17; 95 % CI, 0.98 to 4.79; P = 0.05). Similar results were seen for ampullary adenocarcinoma stratification by histological subtype (P = 0.04) and histomolecular phenotype (P = 0.02). Within poorly differentiated ampullary adenocarcinomas only the 92-gene classifier demonstrated statistically significant differences in RFS and OS (P < 0.05).
  
  
  
  Prognostic stratification of ampullary adenocarcinoma was similar for the 92-gene classifier, histological subtype, and histomolecular phenotype. The 92-gene classifier provides an unbiased standardized molecular-based approach to stratify ampullary tumors.
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Unit 426, 1515 Holcombe Blvd, Unit 421, Houston, TX, 77030, USA. MOverman@mdanderson.org.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Overman
authors.affiliation: Biotheranostics, Inc., 9620 Towne Centre Drive, Suite 200, San Diego, CA, 92121, USA.
authors.forename: Harris S
authors.initials: HS
authors.lastname: Soifer
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Unit 426, 1515 Holcombe Blvd, Unit 421, Houston, TX, 77030, USA.
authors.forename: Aaron Joel
authors.initials: AJ
authors.lastname: Schueneman
authors.affiliation: Houston Methodist Cancer Center, Houston Methodist Research Institute Methodist, Houston, TX, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Ensor
authors.affiliation: Anatomic Pathology, Emory University School of Medicine, H180-B EUH, Atlanta, GA, 30332, USA.
authors.forename: Volkan
authors.initials: V
authors.lastname: Adsay
authors.affiliation: Anatomic Pathology, Emory University School of Medicine, H180-B EUH, Atlanta, GA, 30332, USA.
authors.forename: Burcu
authors.initials: B
authors.lastname: Saka
authors.affiliation: Anatomic Pathology, Emory University School of Medicine, H180-B EUH, Atlanta, GA, 30332, USA.
authors.forename: Nastaran
authors.initials: N
authors.lastname: Neishaboori
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Unit 426, 1515 Holcombe Blvd, Unit 421, Houston, TX, 77030, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 085, Houston, TX, 77030, USA.
authors.forename: Huamin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Biotheranostics, Inc., 9620 Towne Centre Drive, Suite 200, San Diego, CA, 92121, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Schnabel
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Unit 426, 1515 Holcombe Blvd, Unit 421, Houston, TX, 77030, USA.
authors.forename: Gauri
authors.initials: G
authors.lastname: Varadhachary
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000235:genetics; D003138:Common Bile Duct Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D014408:Biomarkers, Tumor
keywords: 92-gene assay; Adenocarcinoma; Ampullary; Biomarker; Gene expression profiling; Prognostic; Subclassification