Three-Gene Immunohistochemical Panel Adds to Clinical Staging Algorithms to Predict Prognosis for Patients With Esophageal Adenocarcinoma

Author:

Ong Chin-Ann J.1,Shapiro Joel1,Nason Katie S.1,Davison Jon M.1,Liu Xinxue1,Ross-Innes Caryn1,O'Donovan Maria1,Dinjens Winand N.M.1,Biermann Katharina1,Shannon Nicholas1,Worster Susannah1,Schulz Laura K.E.1,Luketich James D.1,Wijnhoven Bas P.L.1,Hardwick Richard H.1,Fitzgerald Rebecca C.1

Affiliation:

1. Chin-Ann J. Ong, Xinxue Liu, Caryn Ross-Innes, Maria O'Donovan, Susannah Worster, Laura K.E. Schulz, and Rebecca C. Fitzgerald, Hutchison/MRC Research Centre; Nicholas Shannon, Cambridge Research Institute; Richard H. Hardwick, Addenbrooke's Hospital, Cambridge, United Kingdom; Joel Shapiro, Winand N.M. Dinjens, Katharina Biermann, and Bas P.L. Wijnhoven, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, the Netherlands; and Katie S. Nason, Jon M. Davison, and James D. Luketich,...

Abstract

Purpose 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. Patients and 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). Conclusion 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.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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