Peptides 25 (2004) 771–777 TFF3 expression at the esophagogastric junction is increased in gastro-esophageal reflux disease (GERD) Ulrich Peitz a,∗ , Irina Kouznetsova b , Thomas Wex a , Ingrid Gebert a , Michael Vieth c , Albert Roessner c , Werner Hoffmann b , Peter Malfertheiner a a Department of Gastroenterology, Hepatology, and Infectiology, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany b Institute of Molecular Biology and Medical Chemistry, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany c Institute of Pathology, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany Received 28 October 2003; accepted 7 January 2004 Abstract At the gastric cardia, the molecular mechanisms of inflammation and metaplasia are incompletely understood. Thus, the aim of this study was to determine the expression of TFF1, TFF2 and TFF3 at this site and correlate these data with Helicobacter pylori infection or gastro-esophageal reflux disease (GERD). In 27 patients without intestinal metaplasia at the cardia, endoscopic biopsies were obtained for histology and RT-PCR. TFF1 and TFF2 were expressed in all cardia samples. TFF3 expression was significantly more frequent at the cardia (n = 15/24) than in the corpus (n = 2/26). TFF3 expression at the cardia was mainly observed in GERD patients, and there was a clear tendency towards higher interleukin-8 (IL-8) transcription levels; whereas TFF3 expression was not correlated with the H. pylori status or to tumor necrosis factor- (TNF-) expression. The expression of TFF3 at the cardia may represent an adaptation to GERD and precede the development of Barrett’s esophagus. © 2004 Elsevier Inc. All rights reserved. Keywords: TFF domain; Trefoil factor; Esophagogastric junction; Gastro-esophageal reflux disease; Helicobacter pylori; Intestinal metaplasia 1. Introduction The esophagogastric junction is a site with a high preva- lence of inflammation and intestinal metaplasia, and a rapidly increasing incidence of adenocarcinoma [6]. Be- side representing the border between esophageal squamous and gastric columnar epithelium, it is a transitional zone between two organs with different causes of inflammation. In the esophagus, gastro-esophageal reflux disease (GERD) is the predominant cause, whereas Helicobacter pylori infection is the leading pathogen responsible for gastri- tis. In both organs, a temporal sequence of inflammation, intestinal metaplasia, and eventually adenocarcinoma is observed. In the stomach, the risk of carcinoma is related to the anatomical distribution of gastritis. Pangastritis and corpus-predominant gastritis are linked with hypoaciditiy and pose a considerably higher risk for adenocarcinoma than does antrum-predominant gastritis. The underlying molecu- lar mechanisms for the development of intestinal metaplasia ∗ Corresponding author. Tel.: +49-391-6713100; fax: +49-391-6713105. E-mail address: ulrich.peitz@medizin.uni-magdeburg.de (U. Peitz). are incompletely understood [9,17]. The risk of cancer aris- ing from intestinal metaplasia differs between esophagus and stomach: Intestinal metaplasia in the esophagus, called specialized intestinal metaplasia or Barrett’s mucosa, in- creases the risk by a factor of around 30 [8,30], whereas gastric intestinal metaplasia implicates a risk of adenocar- cinoma that is only about two- to six-fold [20,24]. While esophageal specialized intestinal metaplasia is considered a premalignant lesion, some authors regard gastric intestinal metaplasia merely as a marker of an underlying still unde- fined premalignant condition [24]. The prognostic signifi- cance of intestinal metaplasia at the gastric cardia, adjacent to the esophagogastric junction, is not defined. Epidemiolog- ical and clinical data have yielded conflicting results on the interference of GERD and H. pylori infection as causes of inflammation and metaplasia at the cardia, [12,25,32,33,36]. To elucidate the pathway from inflammation towards in- testinal metaplasia at the esophagogastric junction, mark- ers of intestinal differentiation are of particular interest. By histopathology, mucin-containing goblet cells are the hall- mark of intestinal metaplasia. These cells are interspersed among columnar mucous cells. The glandular structure of 0196-9781/$ – see front matter © 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.peptides.2004.01.018