Oesophageal adenocarcinoma and gastric cancer: should we mind the gap?

Key Points There has been a dramatic increase in the incidence of oesophageal adenocarcinoma (OAC) and intestinal-type gastric cancer (GC) arising near the gastric–oesophageal junction (GOJ). OAC and intestinal-type GC share many common molecular features. OAC and intestinal-type GC are derived from the inflammation–metaplasia cascade that occurs in the oesophageal epithelium in OAC and in the gastric epithelium in intestinal-type GC. Barrett oesophagus and OAC may originate from gastric stem cells derived from the cardia. This Review discusses our current understanding of oesophageal adenocarcinoma and intestinal-type gastric cancer, integrating advances from cell-of-origin studies and comprehensive genomic alteration analyses, with the goal of providing insight into the relationships between these two cancers. Over recent decades we have witnessed a shift in the anatomical distribution of gastric cancer (GC), which increasingly originates from the proximal stomach near the junction with the oesophagus. In parallel, there has been a dramatic rise in the incidence of oesophageal adenocarcinoma (OAC) in the lower oesophagus, which is associated with antecedent Barrett oesophagus (BO). In this context, there has been uncertainty regarding the characterization of adenocarcinomas spanning the area from the lower oesophagus to the distal stomach. Most relevant to this discussion is the distinction, if any, between OAC and intestinal-type GC of the proximal stomach. It is therefore timely to review our current understanding of OAC and intestinal-type GC, integrating advances from cell-of-origin studies and comprehensive genomic alteration analyses, ultimately enabling better insight into the relationship between these two cancers.