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Esophageal malignancies are usually encountered in patients over 50 years old and are associated with significant morbidity and mortality. Efforts to improve patient outcomes are slowly shifted towards unravelling the molecular basis of esophageal cancer as this approach could lead to designing individualized treatment protocols and implementing precision medicine paradigms. Our aim was to present recent advances in esophageal adenocarcinoma genomics, epigenetics and molecular biology with regards to their role on disease pathophysiology, patient outcomes and applications to clinical care. Disease progression is correlated with missense mutations and in-frame deletions of EGFR, as well as with upregulation of a variety of genes (CXCL1 CXCL3, GATA6 and DMBT1), microsatellite instability and telomerase overexpression. On the other hand, p53 loss of heterozygosity as well as HER2 and c-MYC amplifications tend to develop in later stages of the disease and are associated with poor prognosis. Downregulation of CDKN2A, e-cadherin, SMAD4, RUNX3 and aneuploidy/tetraploidy are also correlated with unfavorable outcomes. Lastly, p53 immunohistochemistry and methylation panels are already being applied in clinical practice.

Genomics, Epigenetics and Molecular Considerations in Esophageal Adenocarcinoma: What You Need to Know?