Samuels TL, Altman KW, Gould JC, et al. - Given the role of pepsin as a tumor promoter in the larynx and its possible implication in esophageal carcinogenesis, researchers here tested specimens from the esophageal cancer spectrum for pepsin presence. They assayed pepsin-induced carcinogenic changes in an esophageal cell culture model. Reflux and cancer-free esophagi, Barrett esophagus [BE], esophageal adenocarcinoma (EAC), and esophageal cancer lacking association with reflux (squamous cell carcinoma [SCC]) were assessed for pepsin. BE (3/5) and EAC (4/4) samples showed the presence of pepsinogen and proton pump mRNA, but these were not detected in normal adjacent specimens, SCC (0/2), or reflux and cancer-free esophagi. This indicates the common occurrence of local synthesis of pepsin and proton pumps in BE and EAC. These molecules were absent in normal (noncancer) esophagi, SCC, and in vitro data supporting a role for pepsin in reflux-attributed carcinogenic changes in the esophagus.