Cytokeratin immunoreactivity of intestinal metaplasia at normal oesophagogastric junction indicates its aetiology. (Papers).

J-F Flejou (*)

Abstract

Background and aims--Gytokeratin (CK) 7 and 20 patterns are specific for long and short segments of Barrett's oesophagus but their use has not been assessed in intestinal metaplasia arising in macrosCopicallY normal gastro-oesophageal junction (GOJ).

Patients and methods--This study was carried out in a large prospective series of 254 patients who underwent upper endoscopy, had normal gastro-oesophageal anatomy, and who had biopsies of the antrum, fundus, cardia, GOJ, and lower oesophagus. Intestinal metaplasia of the GOJ was typed by histochemistry with high iron diamine-alcian blue staining and by immunohistochemistry nohistochemistry using CK7 and CK20 antibodies. Results were correlated with clinical, endoscopic, and pathological data.

Results--Sixty (23.6%) of our patients presenting with a normal GOJ had intestinal metaplasia. The CK7/CK20 pattern identified two groups of patients: one highly correlated with Barrett's and the other with characteristics of Helicobacter pylon gastritis. The Barrett's type CK7/CK20 pattern was related to a high frequency of gastro-oesophageal reflux symptoms (p<0.02) and normal endoscopic appearance of the stomach (p<0.03). In contrast, the gastric type CK7/CK20 pattern was linked to atrophic (p<0.02) or erythematous (p<0.05) appearance of the stomach (p<0.03), high frequency of H pylon infection (p<0.04), antral inflammation (p<0.006) with atrophy (p<0.02), and intestinal metaplasia (p<0.02).

Conclusion--In patients presenting with intestinal metaplasia in normal appearing GOJ, the cytokeratin pattern identifies two groups of patients, one with features identical to those of long segment Barrett's oesophagus and one with features seen in H pylon gastritis. These data may be used by clinicians and should result in improved endoscopic surveillance strategies targeted specifically at patients at increased risk of Barrett's oesophagus and thus cancer.

Keywords: Barrett's oesophagus; cardia; intestinal metaplasia; cytokeratins

The incidence of oesophageal adenocarcinomas originating from neoplastic transformation of intestinalised metaplastic mucosa, the so-called Barrett's mucosa commonly thought to be a consequence of gastro-oesophageal reflux disease (gord), (1 2) is increasing. (3 4) Identification of Barrett's oesophagus is readily achieved in patients with long segments of intestinal metaplasia by correlating endoscopic and biopsy findings. (5) Difficulties arise when intestinal metaplasia is present in biopsy specimen taken from the gastro-oesophageal junction (GOJ) with ultrashort segments of columnar mucosa or normal appearing squamocolumnar junction (or Z line) at endoscopy. It may be impossible in such cases to distinguish intestinal metaplasia of the distal oesophagus, related to GORD, from intestinal metaplasia of the proximal stomach (cardia) related to multifocal Helicobacter pylori gastritis. As no absolute histological criteria for diagnosing Barrett's mucosa have yet been established, the diagnostic implication of intestinal metaplasia at the normal GOJ with regard to diagnosis of ultrashort segment Barrett's oesophagus remains to be defined. Recently, it was shown by Ormsby and colleagues (6) that the differential reactivity patterns of expression of cytokeratin (CK) subsets 7 and 20 were useful for distinguishing between long or short segment Barrett's mucosa and gastric intestinal metaplasia. (6 7) The pattern of immunoreactivity of CK7 and CK20 has not yet been defined at the normal GOJ. We therefore studied 254 patients who underwent upper endoscopy, had normal gastro-oesophageal anatomy, and had biopsies of the antrum, fundus, cardia, GOJ, and oesophagus, to (1) determine the CK7 and CK20 pattern in GOJ biopsy specimens with intestinal meraplasia, and (2) evaluate the relationships between this pattern and demographic, clinical, endoscopic, and histological data.

Methods

PATIENTS

Patients undergoing gastroscopy from 1998 to 1999 for upper gastrointestinal symptoms, and presenting with an endoscopically normal GOJ were prospectively identified. These patients came from the practice of 11 experienced gastroenterologists working in an academic setting. In each case, the following patient data were obtained: age, sex, weight, and past medical history of ulcer, gastro-oesophageal reflux symptoms (either heartburn or acid regurgitation), and epigastralgia. Drug therapy, smoking history, and alcohol consumption were also recorded.

Exclusion criteria were: past history of oesophagitis or Barrett's …