Phenotypic differences between esophageal and gastric intestinal metaplasia

Abstract

Intestinal metaplasia is a cancer precursor in the esophagus and the stomach. Marked differences exist between the carcinogenic processes in the two locations in terms of natural history and clinical significance. We investigated biopsies from 52 patients with Barrett's esophagus and from 50 patients with gastric intestinal metaplasia in an attempt to throw light on their pathogenic processes. Morphologic characteristics, presence of Helicobacter pylori (H. pylori), and markers of differentiation, inflammation, and proliferation were evaluated by histochemical and immunohistochemical techniques. The area covered by incomplete type of intestinal metaplasia and the proportion of sulfomucins were significantly higher in the esophagus than in the stomach. Immunoreactivity with MUC1, MUC2, MUC5AC, Das-1, cytokeratins 7 and 20, inducible nitric oxide synthase and cyclooxygenase-2 antibodies was also significantly greater in Barrett's esophagus than in gastric intestinal metaplasia. In gastric intestinal metaplasia, the presence of MUC1, MUC5AC, Das-1 and cytokeratin 7 was restricted to areas with the incomplete type of metaplasia. Cell proliferation (Ki-67) was significantly higher in Barrett's esophagus than in gastric intestinal metaplasia. H. pylori was absent in all of the patients with Barrett's esophagus, while it was present in 70% of the patients with gastric intestinal metaplasia. Our observations made clear that Barrett's esophagus shares some phenotypic characteristics with gastric intestinal metaplasia, leading us to suggest that both could arise in response to injuries with eventual carcinogenic potential. However, the progression to more advanced lesions could be modulated by the nature of the carcinogenic insult.

Repeated exposure to acid and bile selectively induces colonic phenotype expression in a heterogeneous Barrett's epithelial cell line

“…32 This has been confirmed by several independent studies. [33][34][35][36][37][38][39] Furthermore, mAbDas-1 can detect colonic metaplasia before the histological appearance of BE, suggesting the existence of a 'Pre-Barrett's' stage. 34,35 The data suggest that expression of CEP preceded histological BE and persisted during development of metaplasia and progression to carcinoma.…”

Immunoreactivity of cytokeratins 7 and 20 in goblet cells and columnar blue cells in patients with endoscopic evidence of Barrett's esophagus

“…Some subsequent studies appeared to reproduce these findings (19,25,30,31) . However, other authors presented discordant results and they concluded that these patterns are not useful to differentiate BE from intestinal metaplasia of the cardia (6,7,13,20,21,27) . In spite of these inconsistencies, these studies produced some outcomes that deserve further consideration.…”

“…Other immunomarkers that have been studied in the intestinal metaplasia of BE include mucins (14,27) and Cdx2 (26) expression. In the mucin studies, AB staining in the columnar cells was not reported, so it was not possible to evaluate mucin reactivity in the columnar blue cells.…”

“…A previous study by ORMSBY et al (24) suggested that specific patterns of CK7/CK20 reactivity could help discriminate between Barrett's esophagus and intestinal metaplasia of the cardia. Other authors tried to reproduce these patterns, but obtained diverse results (6,7,12,13,19,20,21,25,27,30,31) . Until now, the expression of these cytokeratins has not been reported separately in the goblet cells and the columnar blue cells of individual cases, so it has been hard to evaluate whether the two cell types are similar or different in their expression of these proteins.…”

mAb Das-1 is specific for high-risk and malignant intraductal papillary mucinous neoplasm (IPMN)

“…Tissue sections from each lesion were examined with mAb Das-1 using a sensitive immunoperoxidase assay, as described previously. [25][26][27][28] Each experiment also included at least two slides of normal colon and duodenal tissue sections as positive and negative controls, respectively (figure 1A, B). Non-neoplasic pancreatic tissue with or without IPMNrelated pancreatitis and normal pancreatic ducts served as internal controls (figure 1C, starred).…”