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Intestinal metaplasia (IM) is a preneoplastic lesion of the stomach in which there is transdifferentiation of the gastric mucosa to an intestinal phenotype. The caudal-related homeobox gene CDX2 encodes an intestine-specific transcription factor crucial for the regulation of proliferation and differentiation of intestinal cells. In addition, CDX2 is involved in the induction of IM in the stomach. The aim of this study was to access the putative involvement of OCT-1 in the induction of CDX2 expression de novo in gastric mucosa leading to the onset of IM. OCT-1 protein expression was evaluated by immunohistochemistry in 31 biopsies with chronic gastritis, 15 biopsies with foci of IM and adjacent gastric mucosa and 42 gastric carcinomas. Furthermore, we evaluated OCT-1 binding by electrophoretic mobility shift assay and activation of the CDX2 promoter by co-transfecting a CDX2 promoter/reporter construct with an OCT-1 expression vector in two gastric carcinoma cell lines, GP220 and MKN45. Our results show that OCT-1 is expressed in chronic gastritis, particularly when it is adjacent to IM and is expressed in 87% of IM foci. Furthermore, 74% of the gastric carcinomas were positive for OCT-1 and a strong association was observed between OCT-1 expression and intestinal-type carcinoma. We identified that OCT-1 binds to the CDX2 promoter, although we could not see a transactivation effect in gastric carcinoma cell lines. In conclusion, we observed increased OCT-1 expression in IM and in intestinal gastric carcinomas and identified the capacity of OCT-1 to bind to the CDX2 promoter, although we could not demonstrate a direct effect of OCT-1 in the transactivation of CDX2. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Helicobacter pylori (H. pylori) causes gastritis and intestinal metaplasia (IM) that may evolve to gastric carcinoma. Paradoxically, IM leads to clearing of H. pylori, except for some cases in which it persists in damaging the mucosa. The objective of this study was to compare the profile of mucins and type 1 Lewis antigens in IM cases with and without H. pylori. Gastric biopsies (n=32) were double-stained using immunohistochemistry (MUC1, MUC2, MUC5AC, MUC6, Lea, sialyl-Lea, and Leb) and histochemistry for H. pylori. H. pylori was observed in association with IM in 4 of 22 biopsies with IM (complete IM – 6; incomplete IM – 16). The four biopsies with IM and H. pylori displayed a particular pattern of incomplete IM: expression of MUC1 and MUC5AC and little/no expression of MUC2. The 18 biopsies with IM and without H. pylori had high levels of MUC2 expression, regardless of the IM type. The pattern of expression of type 1 Lewis antigens was similar in IM, regardless of the presence or absence of H. pylori. It is concluded that H. pylori is able to colonize incomplete IM whenever it contains foci expressing MUC1 and MUC5AC and no MUC2, independently from Lea, sialyl-Lea and Leb. The results suggest, furthermore, that MUC2 expression affects the ability of H. pylori to colonize IM areas, regardless of the levels of expression of MUC1 and MUC5AC. Copyright © 2002 John Wiley & Sons, Ltd.

The expression of trefoil peptides (TFF1 and TFF2) and mucins (MUC1, MUC2, MUC5AC, and MUC6) has previously been described in gastric polyps. In the present study, the expression profile of these trefoil peptides and mucins was characterized in 96 gastric carcinomas, in an attempt to further the understanding of the histogenesis and cell differentiation of gastric carcinoma. Taking together the co-expression of trefoil peptides and mucins, three phenotypes were defined: complete gastric, incomplete gastric, and non-gastric phenotype. Gastric differentiation (complete and incomplete) was observed in 30 out of 33 (90.9%) diffuse carcinomas and in 38 out of 53 (71.7%) intestinal carcinomas. Non-gastric differentiation was observed in only three (9.1%) diffuse carcinomas and in 15 (28.3%) intestinal carcinomas. The phenotypes observed in intestinal carcinomas were similar to those previously observed in adenomatous polyps, whereas most diffuse carcinomas mimicked the phenotype of hyperplastic polyps. The percentage of cases displaying a non-gastric phenotype was higher, though not significantly, in tumours that had invaded the gastric wall than in T1 tumours, regardless of histotype. It is concluded that gastric-type differentiation is retained in the majority of gastric carcinomas, being more prominent in diffuse than in intestinal carcinomas, and in early than in advanced carcinomas.

The expression of two trefoil peptides (TFF1 and TFF2) and four mucins (MUC1, MUC2, MUC5AC, and MUC6) was evaluated by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) in 29 gastric polyps, 10 hyperplastic and 19 adenomatous, eight of which displayed malignant transformation. The aims of this study were to characterize the expression profile of these molecules in each type of polyp and to investigate possible modifications of the profile during the process of malignant transformation. All hyperplastic polyps displayed immunoreactivity for TFF1, MUC5AC, and MUC1 in more than 75 per cent of the cells. In adenomatous polyps, three main phenotypes could be identified: complete gastric phenotype (co-expression of TFF1 and MUC5AC)—nine cases (47·4 per cent); incomplete gastric phenotype (TFF1-positive and MUC5AC-negative)—seven cases (36·8 per cent); non-gastric (intestinal) phenotype (no expression of TFF1 or MUC5AC)—three cases (15·8 per cent). Data yielded by immunohistochemistry and RT-PCR showed a good correlation for both TFF1 and TFF2. One hyperplastic and seven adenomatous polyps with villous architecture displayed foci of diffuse and intestinal-type carcinoma, respectively; in all of these cases, MUC1 expression and signs of gastric differentiation were observed in both the non-malignant and the carcinomatous component. It is concluded that gastric differentiation is a feature of hyperplastic polyps and of a subset of adenomatous polyps which is shared by early carcinomas arising in some of these polyps, regardless of the histological type of polyp and of carcinoma. Copyright © 1999 John Wiley & Sons, Ltd.

Helicobacter pylori (H. pylori) causes gastritis and intestinal metaplasia (TM) that may evolve to gastric carcinoma. Paradoxically, IM leads to clearing of H. pylori, except for some cases in which it persists in damaging the mucosa. The objective of this study was to compare the profile of mucins and type 1 Lewis antigens in IM cases with and without H. pylori. Gastric biopsies (n=32) were double-stained using immunohistochemistry (MUC1, MUC2, MUC5AC, MUC6, Le(a), sialyl-Le(a), and Le(b)) and histochemistry for H. pylori. H. pylori was observed in association with IM in 4 of 22 biopsies with IM (complete IM - 6; incomplete IM - 16). The four biopsies with IM and H. pylori displayed a particular pattern of incomplete IM: expression of MUC1 and MUC5AC and little/no expression of MUC2. The 18 biopsies with IM and without H. pylori had high levels of MUC2 expression, regardless of the IM type. The pattern of expression of type 1 Lewis antigens was similar in IM, regardless of the presence or absence of H. pylori. It is concluded that H. pylori is able to colonize incomplete IM whenever it contains foci expressing MUCI and MUC5AC and no MUC2, independently from Le(a), sialyl-Le(a) and Le(b). The results suggest, furthermore, that MUC2 expression affects the ability of H. pylori to colonize IM areas, regardless of the levels of expression of MUC1 and MUC5AC.