Samuels TL, et al. - Researchers tested specimens from the esophageal cancer spectrum for pepsin presence for its implication in esophageal carcinogenesis. They assayed pepsin in reflux and cancer free esophagi, Barrett's esophagus [BE], esophageal adenocarcinoma (EAC), and esophageal cancer lacking association with reflux (squamous cell carcinoma [SCC]). BE (3/5) and EAC (4/4) samples, but not normal adjacent specimens, SCC (0/2), or reflux and cancer-free esophagi, showed pepsinogen and proton pump mRNA. They noted induction of BE and EAC markers interleukin 8 and KRT8 and depletion of normal esophageal marker KRT10 expression when human esophageal cells in vitro were treated with pepsin chronically (0.1–1 mg/mL, 4 weeks). These findings support that reflux-attributed carcinogenic changes in the esophagus may be attributed to pepsin.