Surface Mucous Cells Research Articles

Distribution of ghrelin and GHS‐R in the rat gastric mucosa: effects of early weaning and consequences to growth control

During postnatal development, maternal milk is the main source of nutrients, hormones and factors that promote growth and the functional maturation of the gastrointestinal tract. Early weaning is the abrupt interruption of suckling and it changes the development of the stomach, which represents the major site of ghrelin synthesis. In the present study, we evaluated the short‐term effects of early weaning on gastric ghrelin concentration and conducted a detailed investigation on the distribution of growth hormone secretagogue receptor (GHS‐R) in the rat gastric mucosa during the third postnatal week. In addition, we studied whether ghrelin is part of cell proliferation and differentiation control in gastric epithelium, and to that we used a receptor antagonist. We observed an increase of ghrelin immunostained cells in pups submitted to early weaning. After RT‐PCR, we observed that GHS‐R expression was not altered by dietary change and this result was confirmed through Western blot. We also identified GHS‐R immunolabeled cells along the gastric gland. The antagonist [D‐Lys‐3]‐GHRP‐6 reduced DNA synthesis index, as determined by BrdU incorporation followed by immunohistochemistry, but it did not alter mucous neck cell differentiation. Therefore, we found that ghrelin and GHS‐R are distributed in the gastric mucosa during the third postnatal week and that early weaning increased hormone levels in the gastric epithelium, without changing its receptor. We suggest that ghrelin modulation might be involved in the control of cell proliferation, which is essential for stomach growth. Supported by CNPq and FAPESP (2011/17415–3; 2011/07089–1).

Gli1 Deletion Prevents Helicobacter-Induced Gastric Metaplasia and Expansion of Myeloid Cell Subsets

Chronic inflammation in the stomach induces metaplasia, the pre-cancerous lesion that precedes inflammation-driven neoplastic transformation. While Hedgehog signaling contributes to the initiation of some cancers, its role in gastric transformation remains poorly defined. We found that Helicobacter-infected C57BL/6 mice develop extensive mucous cell metaplasia at 6 month but not at 2 months post-infection. Gastric metaplasia coincided with the appearance of CD45+MHCII+CD11b+CD11c+ myeloid cells that were normally not present in the chronic gastritis at 2 months. The myeloid regulatory gene Schlafen-4 was identified in a microarray analysis comparing infected WT versus Gli1 null mice and was expressed in the CD11b+CD11c+ myeloid population. Moreover this same population expressed IL-1β and TNFα pro-inflammatory cytokines. By 6 months, the mucous neck cell metaplasia (SPEM) expressed IL-6, phosphorylated STAT3 and the proliferative marker Ki67. Expression was not observed in Gli1 mutant mice consistent with the requirement of Gli1 to induce this pre-neoplastic phenotype. Ectopic Shh ligand expression alone was not sufficient to induce SPEM, but with Helicobacter infection synergistically increased the histologic severity observed with the inflammation. Therefore Hedgehog signaling is required, but is not sufficient to generate pre-neoplastic changes during chronic gastritis. Gli1-dependent myeloid cell differentiation plays a pivotal role in the appearance of myeloid cell subtypes ostensibly required for SPEM development. Moreover, it suggests that therapies capable of targeting this phenotypic switch might prevent progression to metaplasia, the pre-neoplastic change that develops prior to dysplasia and gastric cancer, which also occurs in other epithelial-derived neoplasias initiated by chronic inflammation.

Establishment of a long-term three-dimensional primary culture of mouse glandular stomach epithelial cells within the stem cell niche

Compared to the small intestine and colon, little is known about stem cells in the stomach because of a lack of specific stem cell markers and an in vitro system that allows long-term culture. Here we describe a long-term three-dimensional (3D) primary gastric culture system within the stem cell niche. Glandular stomach cells from neonatal mice cultured in collagen gel yielded expanding sphere-like structures for 3months. The wall of the gastrospheres consisted of a highly polarized epithelial monolayer with an outer lining of myofibroblasts. The epithelial cells showed a tall columnar cell shape, basal round nuclei, and mucus-filled cytoplasm as well as expression of MUC5AC, indicating differentiation into gastric surface mucous cells. These cells demonstrated the features of fully differentiated gastric surface mucous cells such as microvilli, junctional complexes, and glycogen and secretory granules. Fewer than 1% of cultured epithelial cells differentiated into enteroendocrine cells. Active proliferation of the epithelial cells and many apoptotic cells in the inner lumen revealed the rapid cell turnover in gastrospheres in vitro. This method enables us to investigate the role of signaling between cell–cell and epithelial–mesenchymal interactions in an environment that is extremely similar to the in vivo environment.

Loss of Anterior Gradient 2 (Agr2) Expression Results in Hyperplasia and Defective Lineage Maturation in the Murine Stomach

Recent studies of epithelial tissues have revealed the presence of tissue-specific stem cells that are able to establish multiple cell lineages within an organ. The stem cells give rise to progenitors that replicate before differentiating into specific cell lineages. The mechanism by which homeostasis is established between proliferating stem or progenitor cells and terminally differentiated cells is unclear. This study demonstrates that Agr2 expression by mucous neck cells in the stomach promotes the differentiation of multiple cell lineages while also inhibiting the proliferation of stem or progenitor cells. When Agr2 expression is absent, gastric mucous neck cells increased in number as does the number of proliferating cells. Agr2 expression loss also resulted in the decline of terminally differentiated cells, which was supplanted by cells that exhibited nuclear SOX9 labeling. Sox9 expression has been associated with progenitor and stem cells. Similar effects of the Agr2 null on cell proliferation in the intestine were also observed. Agr2 consequently serves to maintain the balance between proliferating and differentiated epithelial cells.

Cell Reactions in Gastric Tube and Colon Transplants in Stenoses of Esophageal Anastomosis

We studied morphological and cell characteristics of stenosis of esophagogastric and esophagocolonic anastomosis. It was demonstrated that sclerogenesis in the gastric transplants is associated with hypertrophy of leiomyocytes, hyperelastosis foci, degenerative and atrophic modifications of the glands, and foveolar cell hypersecretion. In colonic transplant, collagen synthesis predominates in the esophageal anastomosis and can be associated with proliferation of blood capillaries; hyperplastic reactions of leiomyocytes and elastic fibers are minor, colonocytes exhibit high secretory activity. Differences in the cell reactions of the transplants reflect complex character of the formation of esophageal anastomosis stenosis.

Gastric stem cells and gastric cancer stem cells

The gastric epithelium is continuously regenerated by gastric stem cells, which give rise to various kinds of daughter cells, including parietal cells, chief cells, surface mucous cells, mucous neck cells, and enteroendocrine cells. The self-renewal and differentiation of gastric stem cells need delicate regulation to maintain the normal physiology of the stomach. Recently, it was hypothesized that cancer stem cells drive the cancer growth and metastasis. In contrast to conventional clonal evolution hypothesis, only cancer stem cells can initiate tumor formation, self-renew, and differentiate into various kinds of daughter cells. Because gastric cancer can originate from gastric stem cells and their self-renewal mechanism can be used by gastric cancer stem cells, we review here how critical signaling pathways, including hedgehog, Wnt, Notch, epidermal growth factor, and bone morphogenetic protein signaling, may regulate the self-renewal and differentiation of gastric stem cells and gastric cancer stem cells. In addition, the precancerous change of the gastric epithelium and the status of isolating gastric cancer stem cells from patients are reviewed.

TFF1 is Differentially Expressed in Stationary and Migratory Rat Gastric Epithelial Cells (RGM-1) after in Vitro Wounding: Influence of TFF1 RNA Interference on Cell Migration

Background/Aims: The trefoil factor family (TFF) peptide TFF1 is typically secreted by gastric surface mucous cells. These cells are also the major players in gastric restitution, i.e., repair of the stomach mucosa by cell migration after injury. Methods: An established in vitro model of gastric restitution, i.e., migration of the non-transformed rat gastric cell line RGM-1 after scratch wounding, was investigated by expression profiling of selected genes from separated stationary and migratory cells. Also semi-quantitative immunocytochemistry was performed. Furthermore, RGM-1 cells were transfected with stealth RNAi™ duplexes targeting Tff1 and relative cell migration rates were analyzed. Results: Surprisingly, Tff1 expression was up-regulated in migratory cells. No unequivocal signs of the epithelial-mesenchymal transition were detectable in migratory cells. Transfection of RGM-1 cells with Tff1-siRNAi duplexes negatively influenced migration of these cells. Conclusion: This clearly points to a function of Tff1 as a motogen. A possible up-regulation of TFF1 synthesis in migratory surface mucous cells also in vivo would be an ideal mechanism to specifically enhance gastric restitution only where topologically needed and to minimize eventual negative side effects of TFF1 such as cell scattering and invasiveness.

NHE8 plays important roles in gastric mucosal protection

Sodium/hydrogen exchanger (NHE) 8 is an apically expressed membrane protein in the intestinal epithelial cells. It plays important roles in sodium absorption and bicarbonate secretion in the intestine. Although NHE8 mRNA has been detected in the stomach, the precise location and physiological role of NHE8 in the gastric glands remain unclear. In the current study, we successfully detected the expression of NHE8 in the glandular region of the stomach by Western blotting and located NHE8 protein at the apical membrane in the surface mucous cells by a confocal microscopic method. We also identified the expression of downregulated-in-adenoma (DRA) in the surface mucous cells in the stomach. Using NHE8(-/-) mice, we found that NHE8 plays little or no role in basal gastric acid production, yet NHE8(-/-) mice have reduced gastric mucosal surface pH and higher incidence of developing gastric ulcer. DRA expression was reduced significantly in the stomach in NHE8(-/-) mice. The propensity for gastric ulcer, reduced mucosal surface pH, and low DRA expression suggest that NHE8 is indirectly involved in gastric bicarbonate secretion and gastric mucosal protection.

Stem Cells, Self-Renewal and Cancer of the Gastric Epithelium

The gastric mucosa and its glands show continuous bidirectional self-renewal via differentiation from stem and progenitor cells. Here, two types of gastric units, i.e., fundic and antral units, form delicate homeostatic systems. This review focuses on recent developments concerning the different types of gastric stem cells, the central function of parietal cells as organizing centres of fundic units, the stepwise differentiation of zymogenic cells via trans-differentiation of mucous neck cells, and unexpected differences between fundic and antral surface mucous cells. Within the last years, the central role of Sonic hedgehog (Shh) for correct self-renewal of fundic units has become much clearer. Furthermore, also the knowledge concerning the genesis of gastric cancer increased substantially. Here, chronic inflammation leads to dysregulated differentiation processes and finally to cancer. Remarkable progress has been made particularly concerning the genesis of two metaplastic cell lineages, i.e., the TFF2/spasmolytic polypeptide expressing metaplasia (SPEM) and intestinal metaplasia, which both arise in intestinal-type cancers in fundic units by dysregulated trans-differentiation of the zymogenic cell lineage. Additionally, Shh has been recognized as a target for inflammatory processes and an important player for innate immunity processes. Thus, stem cells, self-renewal, and gastric cancer are intimately linked.

Stem Cells, Self-Renewal and Cancer of the Gastric Epithelium

The gastric mucosa and its glands show continuous bidirectional self-renewal via differentiation from stem and progenitor cells. Here, two types of gastric units, i.e., fundic and antral units, form delicate homeostatic systems. This review focuses on recent developments concerning the different types of gastric stem cells, the central function of parietal cells as organizing centres of fundic units, the stepwise differentiation of zymogenic cells via trans-differentiation of mucous neck cells, and unexpected differences between fundic and antral surface mucous cells. Within the last years, the central role of Sonic hedgehog (Shh) for correct self-renewal of fundic units has become much clearer. Furthermore, also the knowledge concerning the genesis of gastric cancer increased substantially. Here, chronic inflammation leads to dysregulated differentiation processes and finally to cancer. Remarkable progress has been made particularly concerning the genesis of two metaplastic cell lineages, i.e., the TFF2/spasmolytic polypeptide expressing metaplasia (SPEM) and intestinal metaplasia, which both arise in intestinal-type cancers in fundic units by dysregulated trans-differentiation of the zymogenic cell lineage. Additionally, Shh has been recognized as a target for inflammatory processes and an important player for innate immunity processes. Thus, stem cells, self-renewal, and gastric cancer are intimately linked.

Cloning and spatiotemporal expression of pepsinogen and gastric proton pump genes from mandarin fish (Siniperca chuatsi) during early ontogeny

A fully developed stomach, characterized by the secretion of pepsinogens and chlorhydric acid, is vital for digestion and survival of fish larvae. To further understand the functional development of the stomach of mandarin fish (Siniperca chuatsi) during early ontogeny, the temporal and spatial expression of pepsinogens (PG A1, A2 and C), as well as proton pump genes were analyzed in the stomach from 0 to 40 days post-hatch (dph) by reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) techniques. Pepsinogen C cDNA was firstly cloned with a full length of 1,557 bp, which contained a 37-bp 5'-untranslated region (UTR), an open reading frame of 1,164 bp encoding a polypeptide of 387 amino acids (aa) residues and a 356-bp 3'-UTR. RT-PCR analysis revealed a sequential expression mode of three pepsinogens (PG A1, A2 and C) along the ontogeny of the stomach in mandarin fish. Pepsinogen A1 was firstly detected at 4 dph (84 degree-days, dd) ahead of the appearance of gastric glands; pepsinogen A2 appeared at 12 dph (252 dd) and became the predominant form in the stomach after 19 dph (399 dd); pepsinogen C was the latest expressed gene at 14 dph (294 dd). Expression of proton pump at 12 dph (252 dd), coinciding with the expression time of pepsinogen A2 showed an excellent coordinated transcription mode between proton pump and pepsinogens. ISH analysis located the expression of three pepsinogens and α subunit of proton pump in the same gastric gland cells, which confirmed that they belonged to oxynticopeptic cells. In addition, oxynticopeptic cells developed and increased gradually from 14 to 40 dph. No transcripts of pepsinogens or proton pump were detected in surface mucous cells and mucous neck cells of the gastric mucosa. Our results implied the functional development of stomach in mandarin fish was closely related to pepsinogens expression.

Fibroblast Growth Factor 10-Fibroblast Growth Factor Receptor 2b Mediated Signaling Is Not Required for Adult Glandular Stomach Homeostasis

The signaling pathways that are essential for gastric organogenesis have been studied in some detail; however, those that regulate the maintenance of the gastric epithelium during adult homeostasis remain unclear. In this study, we investigated the role of Fibroblast growth factor 10 (FGF10) and its main receptor, Fibroblast growth factor receptor 2b (FGFR2b), in adult glandular stomach homeostasis. We first showed that mouse adult glandular stomach expressed Fgf10, its receptors, Fgfr1b and Fgfr2b, and most of the other FGFR2b ligands (Fgf1, Fgf7, Fgf22) except for Fgf3 and Fgf20. Fgf10 expression was mesenchymal whereas FGFR1 and FGFR2 expression were mostly epithelial. Studying double transgenic mice that allow inducible overexpression of Fgf10 in adult mice, we showed that Fgf10 overexpression in normal adult glandular stomach increased epithelial proliferation, drove mucous neck cell differentiation, and reduced parietal and chief cell differentiation. Although a similar phenotype can be associated with the development of metaplasia, we found that Fgf10 overexpression for a short duration does not cause metaplasia. Finally, investigating double transgenic mice that allow the expression of a soluble form of Fgfr2b, FGF10's main receptor, which acts as a dominant negative, we found no significant changes in gastric epithelial proliferation or differentiation in the mutants. Our work provides evidence, for the first time, that the FGF10-FGFR2b signaling pathway is not required for epithelial proliferation and differentiation during adult glandular stomach homeostasis.

Loss of HGF activator inhibits foveolar hyperplasia induced by oxyntic atrophy without altering gastrin levels

Spasmolytic polypeptide/trefoil family factor 2 expressing metaplasia (SPEM) is induced by oxyntic atrophy and is known as a precancerous or paracancerous lesion. We now have sought to determine whether hepatocyte growth factor (HGF) influences the development of SPEM and oxyntic atrophy. DMP-777, a parietal cell ablating reagent, was administered to HGF activator (HGFA)-deficient mice and wild-type mice. Gastric mucosal lineage changes were analyzed in the DMP-777 treatment phase and recovery phase. Both wild-type and HGFA knockout mice showed SPEM, and there was no difference in SPEM development. However, after cessation of DMP-777, HGFA-deficient mice showed delayed recovery from SPEM compared with wild-type mice. Foveolar cell hyperplasia and the increase in proliferating cells after parietal cell loss were reduced in HGFA-deficient mice. The HGFA does not affect emergence of SPEM. However, the absence of HGFA signaling causes a delay in the recovery from SPEM to normal glandular composition. HGFA also promotes foveolar cell hyperplasia and mucosal cell proliferation in acute oxyntic injury.

Human gastric TFF2 peptide contains an N-linked fucosylated N,N'-diacetyllactosediamine (LacdiNAc) oligosaccharide

In the human stomach, the peptide trefoil factor family 2 (TFF2) is secreted together with the mucin MUC6 by mucous neck cells (MNCs) and antral gland cells. TFF2 is strongly associated with the gastric mucus and promotes gastric restitution. Here, TFF2 was purified from the human corpus and antrum, respectively, by size-exclusion chromatography, and the N-linked glycan structure at N-15 of the mature peptide was determined. As a hallmark, the unusual monofucosylated N,N'-diacetylhexosediamine (tentatively assigned as GalNAcβ1→4GlcNAc, LacdiNAc) modification was detected as the terminal structure of a bi-antennary complex type N-glycan exhibiting also core fucosylation. Replicate analyses did not show microheterogeneities in the fraction of peptide-N-glycosidase F cleaved and permethylated N-glycans when analyzed by matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS). On the glycopeptide level, a minor glycan microheterogeneity was evident in liquid chromatography-electrospray ionization (ESI)-MS, demonstrating the presence of underfucosylated species. The tryptic TFF2 N-glycopeptide p34-39 (LSPHNR N-glycosylated with Fuc3Hex3HexNAc6) was identified by both ESI-tandem mass spectrometry and MALDI-post-source decay analysis. Lectin analyses with the Wisteria floribunda agglutinin indicated the potential presence of LacdiNAc terminating glycans and revealed minor differences between TFF2 from fundic units, i.e. MNCs, and antral units, i.e. antral gland cells. Strikingly, on the level of the primary structure, there was no indication that the formation of the proposed LacdiNAc structure is cis-controlled by a peptidic determinant related to the published sequences.

Foveolar cells phagocytose apoptotic neutrophils in chronic active Helicobacter pylori gastritis

The recognition and removal of apoptotic inflammatory cells by tissue macrophages and non-professional phagocytes, in a process called efferocytosis, is required for resolution of inflammation and is actively anti-inflammatory. We have previously demonstrated phagocytosis of apoptotic neutrophils by tumor cells in human gastric carcinoma, but to date, there have been no studies investigating this process in chronic active Helicobacter pylori gastritis. Biopsy specimens from 28 subjects with or without H. pylori infection and active inflammation were examined and graded according to the updated Sydney system. Light microscopy, electron microscopy, and Terminal Deoxynucleotidyltransferase-Mediated UTP End Labeling staining were used to identify apoptosis. H. pylori infection was detected by histology and by molecular assay in 16 out of 28 cases. DNA from paraffin-embedded gastric biopsies was amplified using primers specific for cagA, for the cag "empty site" as well as for the s and m alleles of vacA. The more virulent cagA-positive strains were found in five out of nine patients with chronic active gastritis. The vacA s1/m1 and s2/m1 genotypes were more common in nine patients with chronic active gastritis, while the vacA s2/m2 genotype was more frequent in seven patients with chronic inactive gastritis. Apoptotic neutrophils were also detected within the cytoplasmic vacuoles of the foveolar cells of nine cases with chronic active gastritis. Transmission electron micrographs revealed further apoptotic neutrophils within spacious phagosomes of foveolar cells in a similar manner to those described in late-phase efferocytosis both in vivo and in vitro. These new observations expand the morphological spectrum of gastritis in patients infected with more virulent H. pylori strains, compatible with an anti-inflammatory role for the gastric epithelial cells in their removal of apoptotic neutrophils during active chronic gastritis.

Gastric Adenocarcinoma With Chief Cell Differentiation

Gastric adenocarcinoma with chief cell differentiation (GA-CCD) has been reported as a new, rare variant of gastric adenocarcinoma. Only 12 cases in Japanese patients have been described to date, but they demonstrate distinct clinicopathologic features. To further characterize these lesions, we have collected 10 additional cases. Patients ranged in age from 44 to 79 years (mean, 64.2 y) with a relatively equal sex distribution (6 women and 4 men). Stratified by race, 4 patients were Hispanic, 2 were White, 2 were African American, 1 was Asian (Chinese), and the race was unknown for 1 patient. All patients presented with gastroesophageal reflux that prompted an endoscopic examination. The majority of GA-CCDs were identified in the fundus (7 of 10, 70%) and the remaining in the cardia (n=3). Grossly, they were solitary and polypoid, ranging in size from 0.2 to 0.8 cm (mean, 0.4 cm). Histologically, all cases were centered in the deep mucosa, with focal involvement of surface foveolar epithelium in 3 (30%) cases but not the submucosa. The tumors consisted of clustered glands and irregular branching cords of oxyntic epithelium. Thin wisps of radiating smooth muscle separated the epithelium, but desmoplasia was distinctly absent in all cases. The oxyntic mucosa was 1 to 2 cells thick and composed of a mixture of mucous neck, parietal, and chief cells. In 7 of 10 (70%) cases, chief cells were the predominant cell type, whereas the remaining 3 cases consisted primarily of mucous neck cells. The nuclei were mildly enlarged with slight nuclear pleomorphism, but no mitotic figures were identified. In addition, necrosis, lymphovascular invasion, and perineural invasion were absent. Immunohistochemically, GA-CCDs were diffusely positive for MUC6 (10 of 10, 100%) and negative for MUC5AC (0%) and MUC2 (0%). Ki-67 immunolabeling demonstrated variable expression, with the highest areas ranging from 0.2% to 10%. Clinical follow-up was available for 9 of 10 (90%) patients and ranged from 6 to 39 months. One patient had persistence of lesion at 6 months because of incomplete removal, whereas the other 8 were disease free. In summary, GA-CCDs are solitary, mucosal lesions of the gastric cardia/fundus that arise in patients from multiple ethnic backgrounds. Considering that patients within this study and those reported previously have had neither true recurrence nor progression of disease, these lesions are best regarded as benign. Consequently, the term GA-CCD is contradictory and we prefer the descriptive term "oxyntic gland polyp/adenoma" until further studies can clarify the pathogenesis of these lesions and their natural history.

IFNγ contributes to the development of gastric epithelial cell metaplasia in Huntingtin interacting protein 1 related (Hip1r)-deficient mice

Huntingtin interacting protein 1 related (Hip1r) is an F-actin- and clathrin-binding protein involved in vesicular trafficking that is crucial for parietal cell function and epithelial cell homeostasis in the stomach. Gastric parietal cells in Hip1r-deficient mice are lost by apoptotic cell death, which leads to a progressive epithelial cell derangement, including glandular hypertrophy, zymogenic cell loss and expansion of a metaplastic mucous cell lineage known as spasmolytic polypeptide-expressing metaplasia (SPEM). The epithelial cell changes are associated with infiltration of inflammatory cells. As inflammatory mediators, such as IFNγ, have been shown to contribute to the development of the gastric epithelial cell metaplasia after Helicobacter infection, we tested whether IFNγ played a role in the spontaneous progressive epithelial metaplasia observed in Hip1r-deficient mice. Hip1r-deficient mice were crossed with IFNγ-deficient mice and single- and double-mutant mice were analyzed at 3 and 12 months of age. Histopathology scoring showed that loss of IFNγ tempered the spontaneous development of metaplastic lesions in Hip1r-deficient mice. Loss of IFNγ was observed to abrogate the glandular hypertrophy evident in Hip1r mutant stomach, although increased epithelial cell proliferation and elevated gastrin levels were not affected by the presence or absence of this pro-inflammatory cytokine. An analysis of cell lineage markers in the double-mutant mice demonstrated that IFNγ specifically affected the development of metaplastic mucous cells in the neck region, whereas the parietal cell, surface mucous cell and zymogenic cell alterations remained similar to the histopathology in the Hip1r mutant. Morphometric analysis showed that IFNγ was required for the mucous cell hypertrophy and hyperplasia observed in Hip1r-deficient mice. Together, these findings demonstrate that IFNγ is critical for the development of the gastric epithelial cell metaplasia that results from parietal cell atrophy in the Hip1r-deficient mice.

Changes of ultrastructure and downregulation of heat shock protein 70 and fibroblast growth factor 2 in gastric mucosa of rats with depressive-like behaviour.

To understand the underlying mechanism of gastric symptoms in patients with depressive disorder. This study tested in the rat depression model evoked with chronic mild stress whether the microstructure gastric mucosa is injured using scanning electronic microscopy and transmission electronic microscopy (TEM). In addition, the expression of heat shock protein 70 (HSP70) and fibroblast growth factor 2 (FGF2) proteins in the gastric mucosa were measured by Western blotting. We found that the gastric epithelial cells were ruptured and the gastric pits were widened in rats with depression. The amount of mucous granules was also reduced in the surface mucous cells. Moreover, parietal cells became active, and the secretory canaliculi were magnified. Expression of HSP70 and FGF2 was reduced in the gastric mucosa. These findings suggested that gastric symptoms in rats with depressive-like behaviour were caused by the injury of the gastric mucosa, AQ1 and HSP70 and FGF2 may be key molecules in the pathogenesis.

Mo1562 Inflammatory Fibroid Polyp of the Stomach: Clinical and Pathologic Characteristics of 28 Consecutive Cases Seen Over a 44-Month Period

Purpose: Gastric adenomas of intestinal differentiation are much more common than the more recently described adenomas of gastric differentiation. The purpose of this study was to compare the incidence and age at which adenomas of gastric phenotype occur compared to the more common intestinal type gastric adenomas. Methods: We used a large national pathology database of patients who undergo upper endoscopy at community-based surgery centers to determine the relative prevalence and associations of gastric foveolar adenomas, pyloric gland adenomas, and intestinal type adenomas. We extracted pertinent demographic, clinical, endoscopic, and histopathologic information from all patients who had a diagnosis of one of these three types of gastric polyps between 1/1/2008 and 11/1/2011. Frequency distributions and simple odd ratios were used to determine the significance of the associations. Results: From a total of 640,991 patients who underwent upper endoscopy (median age 58 years; 59.8% women), we identified a total of 549 with a diagnosis of gastric adenoma. Of those 443 (81%) were intestinal type, 77 (14%) were foveolar adenomas, and 29 (5%) were pyloric gland adenomas. In each case, the diagnosis was made on H&E stain. Intestinal-type gastric adenomas resembled colonic adenomas with loss of mucin, enlarged and elongated pseudostratified nuclei, and typically associated intestinal metaplasia with Paneth cells. Pyloric gland adenomas were composed of densely packed pyloric glands lined by cuboidal or short columnar cells, and a, typically, unremarkable surface epithelium. Foveolar adenomas featured a surface-predominant villous or papillary architecture with larger than normal foveolar cells and elongated nuclei. There was no significant difference between the median age of the different type of polyps (72 years for intestinal type, 77 for foveolar, and 73 for pyloric gland). There was, however, a significant predominance of women (86.2%) among pyloric gland adenomas (OR=3.86, p<0.01), but not among foveolar adenomas (55.8% women). A small fraction of the study group was known to have FAP (3.4% of intestinaltype adenomas, 2.6% of foveolar adenomas, and none of pyloric gland adenomas). Conclusion: Among a large nationwide population with endoscopy and biopsy for gastric adenomas, intestinal-type adenomas predominate, but almost 20% are of gastric phenotype and may be under-recognized. Our data also reaffirms previous studies that demonstrate a female predominance among pyloric gland adenomas.

Mo1561 The Gastric Phenotype Adenomas (Foveolar and Pyloric Gland Adenomas): Incidence at a National Reference GI Practice

Purpose: Gastric adenomas of intestinal differentiation are much more common than the more recently described adenomas of gastric differentiation. The purpose of this study was to compare the incidence and age at which adenomas of gastric phenotype occur compared to the more common intestinal type gastric adenomas. Methods: We used a large national pathology database of patients who undergo upper endoscopy at community-based surgery centers to determine the relative prevalence and associations of gastric foveolar adenomas, pyloric gland adenomas, and intestinal type adenomas. We extracted pertinent demographic, clinical, endoscopic, and histopathologic information from all patients who had a diagnosis of one of these three types of gastric polyps between 1/1/2008 and 11/1/2011. Frequency distributions and simple odd ratios were used to determine the significance of the associations. Results: From a total of 640,991 patients who underwent upper endoscopy (median age 58 years; 59.8% women), we identified a total of 549 with a diagnosis of gastric adenoma. Of those 443 (81%) were intestinal type, 77 (14%) were foveolar adenomas, and 29 (5%) were pyloric gland adenomas. In each case, the diagnosis was made on H&E stain. Intestinal-type gastric adenomas resembled colonic adenomas with loss of mucin, enlarged and elongated pseudostratified nuclei, and typically associated intestinal metaplasia with Paneth cells. Pyloric gland adenomas were composed of densely packed pyloric glands lined by cuboidal or short columnar cells, and a, typically, unremarkable surface epithelium. Foveolar adenomas featured a surface-predominant villous or papillary architecture with larger than normal foveolar cells and elongated nuclei. There was no significant difference between the median age of the different type of polyps (72 years for intestinal type, 77 for foveolar, and 73 for pyloric gland). There was, however, a significant predominance of women (86.2%) among pyloric gland adenomas (OR=3.86, p<0.01), but not among foveolar adenomas (55.8% women). A small fraction of the study group was known to have FAP (3.4% of intestinaltype adenomas, 2.6% of foveolar adenomas, and none of pyloric gland adenomas). Conclusion: Among a large nationwide population with endoscopy and biopsy for gastric adenomas, intestinal-type adenomas predominate, but almost 20% are of gastric phenotype and may be under-recognized. Our data also reaffirms previous studies that demonstrate a female predominance among pyloric gland adenomas.