BACKGROUND Routine surveillance for dysplastic epithelium in patients with Barrett's esophagus has markedly improved prognosis. Many patients with short segments of Barrett's mucosa near the esophagogastric junction remain undiagnosed and at risk for the development of Barrett's adenocarcinomas (BA). Sucrase isomaltase (SI), an intestinal enzyme, is highly expressed in intestinal-type Barrett's mucosa and frequently expressed in dysplastic Barrett's mucosa and BA. Sucrose isomaltase is not expressed in normal esophageal or gastric mucosa. Alterations in the p53 tumor suppressor gene are frequent events in dysplastic Barrett's mucosa and BA and result in nuclear protein accumulation. The purpose of this study was to determine the presence or absence of these markers of Barrett's mucosa in adenocarcinoma of the esophagogastric junction or cardia. METHODS Expression of SI and p53 were examined in 40 BAs and 25 cardia adenocarcinomas using immunohistochemical techniques. RESULTS Sucrose isomaltase analysis revealed positive staining in 55% (22/40) of the BAs and 44% (11/25) of the cardia adenocarcinomas. Of 14 cardia adenocarcinomas that were SI negative, 100% (14/14) had no associated Barrett's mucosa. However, in 21 cardia adenocarcinomas with no associated Barrett's mucosa, 7/21 (33%) were SI positive. This suggests that SI-positive tumors may represent BA without the standard definition of Barrett's esophagus being met. P53 was present in 65% of BAs and 64% of cardia adenocarcinomas, demonstrating the importance and similarity of this gene alteration in both tumor types. Staining was positive for SI or p53 in 77% (50/65) of all tumors. Tumors of lower stage expressed SI more often than higher stage tumors. CONCLUSIONS These data suggest that a subset of cardia adenocarcinomas represent BAs. Surveillance endoscopy incorporating additional esophagogastric junction biopsies and assessment of SI or p53 may improve detection of intestinalized Barrett's mucosa and early dysplastic changes.