Non-binary.

Generations of oncologists have been pigeonholing cancers at the esophagogastric junction (EGJ) as arising from either esophageal squamous or gastric columnar epithelium. But what if this entity doesn’t conform to our preconceived histologic dichotomy? This week’s Nature study characterizes a distinct transitional epithelium (TE) at the EGJ that arises during embryonic development. And it appears this TE rejects both gastric and esophageal labels. Cells in the basal layer of the TE (in contrast to those found in either the stomach or esophagus) were found to express KRT7. What else expresses KRT7? Barrett’s esophagus, indicating this metaplastic process in fact arises from TE. They went on to divert bile (i.e. reflux) into the EGJ of mice and witnessed TE proliferation. So who cares about labels, anyway? Well, you may have noticed that EGJ cancers have been relegated to the back of the struggle bus of GI trials this year—lumped in with one esophageal or gastric trial after another. This evidence supports recognizing this classic anatomic site as a distinct biological entity, and we believe it’s high time EGJ cancers earn a third option in clinical trial designs.