Adenocarcinoma of the GEJ: gastric or oesophageal cancer?

According to WHO (2010) adenocarcinomas of the esophagogastric junction (GEJ) are defined as tumors that cross the most proximal extent of the gastric folds regardless of where the bulk of the tumor lies. In addition, these neoplasms are now classified as esophageal cancers by UICC (2010). Recent studies, however, revealed two types of carcinogenesis in the distal oesophagus and at the GEJ, one of intestinal type (about 80 %) and the other of gastric type (about 20 %). These are characterized by marked differences in morphology, tumor stage at diagnosis, and prognosis. Furthermore, both cancer types show different targetable biomarker expression profiles such as Her2 in the intestinal and EGFR in the non-intestinal pathway indicating new therapy options. Due to the fact that carcinomas of the intestinal pathway were typically associated with Barrett's mucosa which was not the case in the non-intestinal-type tumors, this challenges the paradigm "no goblets no Barrett's". Moreover, even the cancer risk of intestinal-type metaplasia has seriously been questioned by a Danish population-based study where Barrett's mucosa turned out to be only a weak indicator of esophageal and GEJ cancer (1 case in 860 patients years). Thus, two biologically different types of cancer arise at the GEJ-esophageal and gastric type that open distinctive targeted treatment options and also question our current concept about the diagnostics of potential precursor lesions as well as the associated screening and surveillance strategy.