title: Three-gene immunohistochemical panel adds to clinical staging algorithms to predict prognosis for patients with esophageal adenocarcinoma.
abstract: OBJECTIVE
  Esophageal adenocarcinoma (EAC) is a highly aggressive disease with poor long-term survival. Despite growing knowledge of its biology, no molecular biomarkers are currently used in routine clinical practice to determine prognosis or aid clinical decision making. Hence, this study set out to identify and validate a small, clinically applicable immunohistochemistry (IHC) panel for prognostication in patients with EAC.
  
  
  METHODS
  We recently identified eight molecular prognostic biomarkers using two different genomic platforms. IHC scores of these biomarkers from a UK multicenter cohort (N = 374) were used in univariate Cox regression analysis to determine the smallest biomarker panel with the greatest prognostic power with potential therapeutic relevance. This new panel was validated in two independent cohorts of patients with EAC who had undergone curative esophagectomy from the United States and Europe (N = 666).
  
  
  RESULTS
  Three of the eight previously identified prognostic molecular biomarkers (epidermal growth factor receptor [EGFR], tripartite motif-containing 44 [TRIM44], and sirtuin 2 [SIRT2]) had the strongest correlation with long-term survival in patients with EAC. Applying these three biomarkers as an IHC panel to the validation cohort segregated patients into two different prognostic groups (P < .01). Adjusting for known survival covariates, including clinical staging criteria, the IHC panel remained an independent predictor, with incremental adverse overall survival (OS) for each positive biomarker (hazard ratio, 1.20; 95% CI, 1.03 to 1.40 per biomarker; P = .02).
  
  
  CONCLUSIONS
  We identified and validated a clinically applicable IHC biomarker panel, consisting of EGFR, TRIM44, and SIRT2, that is independently associated with OS and provides additional prognostic information to current survival predictors such as stage.
authors.affiliation: Hutchison/MRC Research Centre, Cambridge, UK.
authors.forename: Chin-Ann J
authors.initials: CA
authors.lastname: Ong
authors.forename: Joel
authors.initials: J
authors.lastname: Shapiro
authors.forename: Katie S
authors.initials: KS
authors.lastname: Nason
authors.forename: Jon M
authors.initials: JM
authors.lastname: Davison
authors.forename: Xinxue
authors.initials: X
authors.lastname: Liu
authors.forename: Caryn
authors.initials: C
authors.lastname: Ross-Innes
authors.forename: Maria
authors.initials: M
authors.lastname: O'Donovan
authors.forename: Winand N M
authors.initials: WN
authors.lastname: Dinjens
authors.forename: Katharina
authors.initials: K
authors.lastname: Biermann
authors.forename: Nicholas
authors.initials: N
authors.lastname: Shannon
authors.forename: Susannah
authors.initials: S
authors.lastname: Worster
authors.forename: Laura K E
authors.initials: LK
authors.lastname: Schulz
authors.forename: James D
authors.initials: JD
authors.lastname: Luketich
authors.forename: Bas P L
authors.initials: BP
authors.lastname: Wijnhoven
authors.forename: Richard H
authors.initials: RH
authors.lastname: Hardwick
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fitzgerald
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D015331:Cohort Studies; D066246:ErbB Receptors / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D056565:Sirtuin 2 / Q000378:metabolism; D015996:Survival Rate; D000070584:Tripartite Motif Proteins; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C540677:TRIM44 protein, human; D000070584:Tripartite Motif Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; C474199:SIRT2 protein, human; D056565:Sirtuin 2