Molecular signature of esophageal adenocarcinoma derived from microarray analysis of paraffin-embedded specimens predicts systemic recurrence following resection

Abstract

4563 Introduction: Surveillance endoscopy in patients with Barrett’s esophagus has resulted in the diagnosis of an increasing number of early-stage adenocarcinomas. Surgical resection alone is curative in the majority of these patients, yet some will succumb to systemic disease. We hypothesize that among patients with early esophageal adenocarcinoma, there are distinct molecular signatures of tumors that are associated with systemic recurrence and those that are cured with resection alone. Methods: From a total of 36 patients with early-stage adenocarcinoma (T1–3, less than or equal to 4 involved nodes), 20 who were alive and without recurrence at a median follow-up of 61 months after resection alone were compared by microarray analysis with similar stage tumors from 16 patients that developed systemic disease and died at a median of 13 months after esophagectomy. Following microdissection of paraffin-embedded specimens, RNA was isolated, amplified, labeled, and hybridized to Affymetrix U133 Plus 2.0 GeneChips. Results: A T-test with unequal variance assumption identified 328 differentially expressed probe sets (false discovery rate <0.05; p67 mos. vs. 13 mos., respectively; p<0.001). Significant canonical pathway deregulation between long and short survivors included GABA receptor, PDGF, PPAR, IL-6 signaling, oxidative phosphorylation and the pentose phosphate pathway. Conclusion: The molecular signature of early-stage esophageal adenocarcinomas may be able to distinguish patients at increased risk for the development of systemic disease and thereby guide use of adjuvant therapy and the intensity of follow-up. Confirmation of these findings in additional patients should prompt a prospective clinical trial. [Table: see text]