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. 2000 May;46(5):632–638. doi: 10.1136/gut.46.5.632

The pathogenesis of duodenal gastric metaplasia: the role of local goblet cell transformation

R Shaoul 1, P Marcon 1, Y Okada 1, E Cutz 1, G Forstner 1
PMCID: PMC1727926  PMID: 10764705

Abstract

BACKGROUND AND AIMS—Gastric metaplasia is frequently seen in biopsies of the duodenal cap, particularly when inflamed or ulcerated. In its initial manifestation small patches of gastric foveolar cells appear near the tip of a villus. These cells contain periodic acid-Schiff (PAS) positive neutral mucins in contrast with the alcian blue (AB) positive acidic mucins within duodenal goblet cells. Previous investigations have suggested that these PAS positive cells originate either in Brunner's gland ducts or at the base of duodenal crypts and migrate in distinct streams to the upper villus. To investigate the origin of gastric metaplasia in superficial patches, we used the PAS/AB stain to distinguish between neutral and acidic mucins and in addition specific antibodies to immunolocalise foveolar cell mucin MUC5AC, the foveolar cell secretory product, gastric trefoil factor (TFF1), the mature goblet cell mucin MUC2, and MUC2 core antigen.
RESULTS—Cells in focal patches of gastric metaplasia contained secretory granules of both gastric and goblet cell phenotypes. MUC5AC and TFF1 were present as expected in gastric foveolar cells but in addition, MUC2 core antigen, normally present only in the Golgi of intestinal goblet cells, was expressed in secretory granules. Goblet cells in the vicinity of metaplastic patches also expressed both gastric and intestinal antigens. MUC5AC/MUC2 containing goblet cells were most common near the villus tip but were also seen at the base of crypts. Where crypts and Brunner's gland ducts merged they were always seen on the crypt side of the junction. Goblet cells were the only cells to express gastric antigens in these areas. In advanced metaplastic lesions, dual phenotype goblet cells were less evident and fewer cells expressed intestinal mucin antigens.
CONCLUSIONS—We suggest that goblet cells that express both intestinal and gastric antigens may represent local precursors of gastric metaplasia undergoing a transition to foveolar-like cells of mixed phenotype at the site of early metaplastic patches. As metaplasia becomes more widespread, a more pure gastric phenotype emerges. This progression is likely to be controlled by local inflammatory signals.


Keywords: gastric metaplasia; goblet cells; mucin

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Figure 1  .

Figure 1  

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Immunohistochemical localisation of the gastric mucin MUC5AC and gastric trefoil factor (TFF1) in normal antrum and duodenum (A-D), and duodenum containing focal gastric metaplasia (E, F, and H). (A) MUC5AC, normal antrum; (B) MUC5AC, normal duodenum; (C) TFF1 in the same area of the antral biopsy shown in (A);(D) TFF1, normal duodenum, arrow marks a weakly stained goblet cell; (E, F) serial sections of duodenum containing gastric metaplasia ((E) MUC5AC, (F) TFF1), arrows show positively stained areas; (G, H) serial sections stained by PAS/AB (G) and for MUC5AC (H), arrows point to sites of PAS staining; in (G), all goblet cells were AB positive.    

Figure 2  .

Figure 2  

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Distribution of intestinal mucin MUC2 and gastric mucin MUC5AC in serial sections of antrum and duodenum. (A) MUC2, normal antrum; (B) MUC5AC, normal antrum; (C, D) duodenum containing focal gastric metaplasia ((C) MUC2; (D) MUC5AC).

Figure 3  .

Figure 3  

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Electron micrograph of two areas within a patch of focal metaplasia. In each, Lum=lumenal surface. (A) Gob, a cell containing mucous secretory granules typical of intestinal goblet cells; G, mucus secretory granules typical of gastric foveolar cells. (B) Arrow shows single cell containing granules typical of both gastric and intestinal phenotypes; G, mucus granules with gastric phenotype.

Figure 4  .

Figure 4  

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Immunolocalisation of MUC2 core antigen. (A) Normal duodenum showing staining for core antigen in the supranuclear Golgi region at the base of the goblet cell storage granule mass (arrow); (B) absence of core antigen staining in normal antrum; (C) MUC2 core antigen in the secretory granules of cells in a focal area of duodenal gastric metaplasia (arrow); (D) MUC5AC staining of area shown in (C).

Figure 5  .

Figure 5  

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Expression of gastric and intestinal markers in cells near a patch of focal duodenal gastric metaplasia. Panels A-D are serial sections of well oriented mucosa showing entire crypt-villus unit plus junctional zone between crypts and Brunner's gland ducts. (A) MUC5AC; (B) gastric trefoil factor (TFF1); (C) MUC2; (D) human defensin 5 (HD5). The arrows in (A), (B), and (C) show an area of metaplasia. In (D), the arrow shows a positively stained Paneth's cell at the base of a crypt. (E, F) Serial sections at higher magnification of the junctional zone between Brunner's gland ducts and crypts ((E) MUC5AC; (F) MUC 2). The arrows show a stained cell of indeterminate phenotype at the junction of crypt and duct.

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