Utilization of Cytokeratins 7 and 20 Does Not Differentiate between Barrett's Esophagus and Gastric Cardiac Intestinal Metaplasia

Abstract

Long segment Barrett's esophagus (LSBE) is a recognized risk factor for the development of esophageal dysplasia and carcinoma. However, the risk of dysplasia arising within intestinal metaplasia below a normal-appearing Z-line (i.e., in native cardiac mucosa) is unknown. Regular endoscopic surveillance is required in patients with LSBE and is frequently performed in short segment BE (SSBE), but the need for surveillance in cardiac intestinal metaplasia (CIM) is unknown. Unfortunately IM arising in SSBE and immediately below a normal Z-line can be indistinguishable histologically on H&E stains. Previous reports suggest that the appearance of superficial CK20 immunohistochemical staining accompanied by intermediate and deep CK7 positivity is characteristic of BE, whereas CIM specimens show superficial and deep CK20 positivity and weak to absent CK7 staining. We hypothesized that CK7/20 immunostaining of metaplastic biopsies from the esophagus and stomach would allow complete differentiation of these two entities when correlated with the endoscopic appearance. We undertook an evaluation of gastric and esophageal specimens to determine whether these characteristics were valid. Cases of both BE (long and short segment) and CIM, as well as cases of gastric cardiac biopsies lacking IM, were evaluated for CK7 and CK20 and correlated with the endoscopic appearance. We observed that, although the "Barrett's" pattern of CK7/20 was maintained for many cases of BE, the sensitivity and specificity were only moderate (65% and 56%, respectively). The pattern of staining for the CIM was variable, i.e., some cases showed a CK7/20 Barrett's pattern despite a normal appearance at endoscopy. The differences between this and previous studies may be due to inaccurate visualization of SSBE on endoscopy, the development of very early SSBE cases, inter-observer variability, fixation differences, or antibody differences. Whatever the cause of the differences, if results between laboratories are not comparable, CK7/20 immunostaining cannot be used to differentiate reliably between IM present in biopsy specimens taken from above versus below the Z-line. However, further studies should be performed to determine whether the presence or absence of a Barrett's pattern of CK7/20 immunostaining could predict progression to dysplasia or carcinoma.

Barrett’s Esophagus and Cardiac Intestinal Metaplasia: Two Conditions within the Same Spectrum

“…These results are similar to some previous reports (5,25), but were not always reproducible. The apparent discrepancy between studies may be due to a number of factors, including inaccurate visualization of short segment BE on endoscopy, interobserver variability, tissue fixation differences, and immunohistochemical staining differences (eg, antigen retrieval methods (25). Another important factor is the anatomical location from which the biopsy was taken, because biopsies obtained distal to the cardia have a significantly lower likelihood of showing a BE pattern.…”

“…These data support our hypothesis that the development of BE is a progression from CIM to BE, then to dysplasia. Further studies should be performed to determine whether the presence or absence of a BE pattern of CK7/CK20 immunostaining could predict progression to dysplasia or carcinoma, as previously suggested (25).…”

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.…”

“…SHEARER et al (31) mentioned that similar patterns of CK7/CK20 expression were frequently observed in adjacent areas with and without goblet cells. 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.…”

“…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.…”