Phenotype of Barrett's Esophagus and Intestinal Metaplasia of the Distal Esophagus and Gastroesophageal Junction

Abstract

The pathogenesis of short segment Barrett's esophagus (SSBE) and intestinal metaplasia (IM) of the gastroesophageal junction (IMGEJ) are poorly understood. Also, these conditions are difficult to distinguish from one another based solely on endoscopic and pathologic criteria. Therefore, the aim of this study was to evaluate the immunophenotypic features of SSBE and IMGEJ and to compare the results with lesions of known etiologies: long segment BE (LSBE) caused by reflux disease and Helicobacter pylori-induced IM of the gastric antrum (IMGA). Routinely processed mucosal biopsy specimens from 11 patients with LSBE, 17 with SSBE, 10 with IMGEJ, 16 with IMGA, 17 with a normal nonmetaplastic GEJ, and 7 patients with a normal gastric antrum were immunohistochemically stained with monoclonal antibodies to: Das1, an antibody shown to react specifically with colonic goblet cells; 45M1, an antibody that recognizes the M1 gastric mucin antigen; and cytokeratin (CK) 7 and 20, antibodies that have previously been reported to show specific staining patterns in BE versus IMGA. Also evaluated was nonintestinalized mucinous epithelium from LSBE, SSBE, and also the normal GEJ and gastric antrum. LSBE, SSBE, and IMGEJ showed similar prevalences of Das1 (91% versus 88% versus 100%) and 45M1 reactivity (100% versus 100% versus 100%), and a similar pattern of CK7/20 reactivity (diffuse strong CK7 staining of the surface and crypt epithelium, and strong surface and superficial crypt CK20 staining) (91% versus 94% versus 90%). In contrast, although 45M1 reactivity in IMGA (93%) was similar to that of the other three groups, IMGA showed a significantly lower prevalence of Das positivity (13%, p < 0.001), and only a 14% prevalence of the CK7/20 staining pattern that was predominant in the other three groups (p < 0.001). Das1, 45M1, and CK7/20 staining were similar in nonintestinalized "cardia-type" mucinous epithelium from LSBE, SSBE, and the GEJ, but all were distinct from the normal gastric antrum. In summary, the immunophenotypic features of SSBE and IMGEJ are similar and closely resemble those seen in classic LSBE, but are distinct from IMGA. This may indicate that IM in LSBE, SSBE and at the GEJ have similar biologic properties. Based on our data, SSBE and IMGEJ cannot be distinguished on the basis of their immunophenotype.

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.…”

“…CK8/18 has been observed in multi-layered epithelium in BE by immunocytochemistry. 51 This focal multi-layered epithelium within BE comprises cells that concurrently express both squamous and columnar cytokeratin markers, much like the esophageal mucosal gland duct epithelium 34 and the non-neoplastic telomerase-immortalized Barrett's cell line, (BAR-T). 52 We utilized the BAR-T cell line as a model to identify the specific cell phenotype in a heterogeneous 52 cell population that could demonstrate molecular and/or cell phenotypic changes following chronic exposure to acid and bile.…”

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.…”

“…MOHAMMED et al (21) identified the Barrett pattern in 55% of biopsies from inflamed or normal cardiac mucosa without evidence of intestinal metaplasia. GLICKMAN et al (13) noted that the immunophenotypes of the cardiac mucosa in patients with long-segment BE, shortsegment BE and normal esophagogastric junction were similar for Das-1 and CK7/CK20, but they were different from those of the gastric antral mucosa. DeMEESTER et al (6) observed that the cardiac mucosa showed the Barrett pattern in 85% of their cases.…”

“…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.…”