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

• Published in: Journal of clinical oncology Vol. 31; no. 12; pp. 1576 - 1582
• Main Authors: ONG, Chin-Ann J, SHAPIRO, Joel, WORSTER, Susannah, SCHULZ, Laura K. E, LUKETICH, James D, WIJNHOVEN, Bas P. L, HARDWICK, Richard H, FITZGERALD, Rebecca C, NASON, Katie S, DAVISON, Jon M, XINXUE LIU, ROSS-INNES, Caryn, O'DONOVAN, Maria, DINJENS, Winand N. M, BIERMANN, Katharina, SHANNON, Nicholas
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 20.04.2013
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Algorithms; Biological and medical sciences; Biomarkers, Tumor - metabolism; Carrier Proteins - metabolism; Cohort Studies; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - mortality; Esophageal Neoplasms - pathology; Esophagus; Female; Follow-Up Studies; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunoenzyme Techniques; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Grading; Neoplasm Staging; Original Reports; Prognosis; Receptor, Epidermal Growth Factor - metabolism; Sirtuin 2 - metabolism; Survival Rate; Tumors; Young Adult; Human; Immunohistochemistry; Prognosis; Staging; Esophageal disease; Stage classification; Prediction; Patient; Malignant tumor; Algorithm; Decision tree; Esophagus cancer; Anatomic pathology; Cancerology; Gene; Digestive diseases; Esophagus adenocarcinoma; Genetics; Predictive factor; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2012.45.9636

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. 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). 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). 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.