Elsevier

Human Pathology

Volume 33, Issue 6, June 2002, Pages 660-668
Human Pathology

Original Contributions
Barrett's esophagus is characterized by expression of gastric-type mucins (MUC5AC, MUC6) and TFF peptides (TFF1 and TFF2), but the risk of carcinoma development may be indicated by the intestinal-type mucin, MUC2*,**

https://doi.org/10.1053/hupa.2002.124907Get rights and content

Abstract

Barrett's esophagus (BE) consists of metaplastic epithelium of the esophagus, generally diagnosed by mucin histochemistry. We aimed to determine which mucins were expressed in BE, and to relate their expression to BE pathology. Archival biopsies of 4 patient groups were selected, based on standard histochemistry: BE without inflammation, BE with inflammation, ulcerating BE, and BE with dysplasia. Sections were stained by immunohistochemistry for secretory mucins (MUC2, MUC5AC, MUC5B, and MUC6), the proliferation marker Ki-67, and mucin-associated trefoil factor family (TFF) peptides (TFF1, TFF2, and TFF3). MUC5AC and TFF2 were expressed at similar high levels in each clinical group. Intestinal metaplasia (IM), detected both histochemically and by the intestinal mucin MUC2, was lowest in inflamed BE. The expression of the intestinal-type TFF3 did not differ among the groups. Ulcerating BE was distinguished by very low expression of MUC6 and MUC5B, but very high expression of TFF1. Proliferation was not different among the groups. In the total group of BE patients, H. pylori infection of the stomach correlated with decreased TFF2 expression in the BE epithelium. We conclude that BE is best characterized by the specific expression of the gastric-type markers, MUC5AC, MUC6, TFF1, and TFF2. Ulcerating BE constitutes the most distinguished group with respect to mucin and TFF expression. Of the intestinal markers, MUC2 is very specific for IM in BE, whereas TFF3 is not a marker for IM. The low occurrence of IM in inflamed BE suggests that these patients may have the lowest risk of developing carcinoma. Hum Pathol 33:660-668. Copyright 2002, Elsevier Science (USA). All rights reserved.

Section snippets

Patients

Tissue samples were retrieved from archives of patients with endoscopic evidence of BE. The biopsy specimens were collected between January 1993 and November 1999 at the University Hospital Leuven, Belgium. BE pathology and H. pylori status in stomach and gastric pathology (based on at least 2 stomach biopsies) were retrieved from clinical records. Based on hematoxylin and eosin staining of sections of the biopsy specimens, tissue samples of 71 patients were divided into 4 groups: nonactively

Patients

The mean age of the patients was 64.5 years (n = 71; range, 22 to 91 years) (Table 2).

. Patient numbers of the clinical groups (n = 71)

H. pyloriNegativePositive
Noninflamed BE10 (7/3)10 (6/4)
Actively inflamed BE8 (7/1)8 (7/1)
BE with ulcer10 (6/4)8 (7/1)
BE with dysplasia8 (6/2)9 (8/1)

Note: Sex ratio is indicated (m/f). H. pylori status refers to the presence of the bacterium in antrum biopsy specimens of the patients.

The mean age of the clinical groups did not differ significantly (t test). The age

Discussion

Our study was the first to investigate 7 protein markers for gastrointestinal secretory phenotypes against a well-defined clinical background representing the early, premalignant stages of BE. When compared to other regions of the gastrointestinal tract, the BE epithelium showed a MUC-type mucin and TFF expression resembling that of normal human stomach epithelium, in which the expression of these MUCs and TFFs has been demonstrated previously.4, 13, 17, 18, 19, 20, 21, 22 In BE, MUC5AC

Acknowledgements

The authors acknowledge the pilot work on BE done by Jan-Willem Van Klinken and Jos Boshuizen, which guided our thoughts in the setup of this study. They thank their international colleagues who provided antibodies: G. Offner (BGBM), C. de Bolós (anti-M6.1), A. Giraud (pS2 and hSP), and D.K. Podolsky (HM:169 and WE9).

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    *

    Supported by grants from the Netherlands Digestive Diseases Foundation, Irene Foundation, Jan Dekker/Ludgardine Bouman Foundation, and Foundation “De Drie Lichten.”

    **

    Address correspondence and reprint requests to Jan Dekker, Laboratory of Pediatrics, Erasmus University, Rm. EE-15-71A, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.

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