intrinsic-factor and Precancerous-Conditions

Surveillance of intestinal metaplasia (IM) of the gastric mucosa should be limited to patients at high risk of gastric cancer. Patients with extensive IM are at increased cancer risk; however, the intragastric extent of IM is usually unknown at the time of the initial diagnosis.. To assess the predictive value of clinical, histologic, and serologic parameters for the intragastric extent of IM.. Prospective, multicenter study.. Eighty-eight patients with a previous diagnosis of IM of the gastric mucosa.. Surveillance gastroscopy with extensive random biopsy sampling.. Biopsy specimens were evaluated according to the Sydney classification system. In addition, serologic testing of Helicobacter pylori and cagA status, pepsinogens I and II, gastrin, and intrinsic factor antibodies was performed. The association between the available parameters and extensive IM was evaluated with logistic regression analysis.. In 51 patients (58%), IM was present in the biopsy specimens from at least 2 intragastric locations. The most important predictors of extensive IM were a family history of gastric cancer, alcohol use > or = 1 unit/d (1 glass, approximately 10 mL or 8 g ethanol), moderate or marked IM of the index biopsy specimen, and a pepsinogen I to II ratio < 3.0. A simple risk score based on these factors could identify extensive IM in 24 of 25 patients (sensitivity 96%).. A prospective cohort study should confirm the proposed risk stratification.. A risk score of clinical, histologic, and serologic parameters can predict extensive intragastric IM and may serve as a practical tool to select patients for surveillance endoscopy in routine clinical practice.

Topics: Adult; Aged; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Proteins; Biopsy; Endoscopy, Gastrointestinal; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Gastric Mucosa; Gastrins; Helicobacter pylori; Humans; Intrinsic Factor; Male; Metaplasia; Middle Aged; Pepsinogen A; Pepsinogen C; Precancerous Conditions; Prognosis; Prospective Studies; Risk Factors; Stomach Neoplasms; Surveys and Questionnaires; Time Factors; Young Adult

Loss of gastric parietal cells is a critical precursor to gastric metaplasia and neoplasia. However, the origin of metaplasia remains obscure. Acute parietal cell loss in gastrin-deficient mice treated with DMP-777 leads to the rapid emergence of spasmolytic polypeptide/trefoil factor family 2 (TFF2)-expressing metaplasia (SPEM) from the bases of fundic glands. We now sought to characterize more definitively the pathway for emergence of SPEM.. Emerging SPEM lineages in gastrin-deficient mice treated with DMP-777 were examined for immunolocalization of TFF2, intrinsic factor, and Mist1, and morphologically with electron microscopy. Emerging SPEM was isolated with laser-capture microdissection and RNA was analyzed using gene microarrays. Immunohistochemistry in mouse and human samples was used to confirm up-regulated transcripts.. DMP-777-induced SPEM was immunoreactive for TFF2 and the differentiated chief cell markers, Mist1 and intrinsic factor, suggesting that SPEM derived from transdifferentiation of chief cells. Microarray analysis of microdissected SPEM lineages induced by DMP-777 showed up-regulation of transcripts associated with G1/S cell-cycle transition including minichromosome maintenance deficient proteins, as well as a number of secreted factors, including human epididymis 4 (HE4). HE4, which was absent in the normal stomach, was expressed in SPEM of human and mouse and in intestinal metaplasia and gastric cancer in human beings.. Although traditionally metaplasia was thought to originate from normal mucosal progenitor cells, these studies indicate that SPEM evolves through either transdifferentiation of chief cells or activation of a basal cryptic progenitor. In addition, induction of metaplasia elicits the expression of secreted factors, such as HE4, relevant to gastric preneoplasia.

Topics: Animals; Atrophy; Basic Helix-Loop-Helix Transcription Factors; beta-Defensins; Carrier Proteins; Cell Cycle Proteins; Cell Transformation, Neoplastic; Chief Cells, Gastric; DNA-Binding Proteins; Epididymal Secretory Proteins; Fetal Proteins; Gastric Fundus; Gastric Mucosa; Gastrins; Humans; Intercellular Signaling Peptides and Proteins; Intrinsic Factor; Metaplasia; Mice; Mice, Inbred C57BL; Mice, Knockout; Microtubule-Associated Proteins; Minichromosome Maintenance Complex Component 3; Mucins; Muscle Proteins; Nuclear Proteins; Parietal Cells, Gastric; Peptides; Precancerous Conditions; Stomach Neoplasms; Trefoil Factor-2

The Authors show and discuss the classification proposed till now for dividing chronic atrophic gastritis into subtypes different in hystological, functional or immunological aspects. In accordance with the more recent reports, the classification into type A, type B and type AB is accepted. Genetical (factor A) and environmental agents (alcohol, smoke, drugs) as well as immunological (parietal and gastrin cell antibodies) and functional abnormalities (duodenogastric reflux), suggested to play a role in the aetiopathogenesis of chronic atrophic gastritis, are also re-examined. Finally, dynamic aspects of chronic atrophic gastritis and its association with anemia and gastric carcinoma are widely reviewed.

Topics: Age Factors; Antibodies; Chronic Disease; Gastritis; Gastritis, Atrophic; Gastroesophageal Reflux; Humans; Intrinsic Factor; Precancerous Conditions; Sex Factors; Smoking; Stomach Neoplasms; Substance-Related Disorders

The prevalence of circulating antibodies to gastric intrinsic factor and parietal cells was examined in 60 patients with histologically proven gastric carcinoma and was found not to differ from the prevalence of these antibodies in control subjects of similar age and sex distribution.Amongst the 60 patients with gastric carcinoma seven were thought to have actual or potential pernicious anaemia. The absence of an increased prevalence of antigastric antibodies in gastric carcinoma indicates that gastritis itself, whether autoimmune or not, is the likely common denominator underlying the predisposition to gastric carcinoma in both pernicious anaemia and chronic atrophic gastritis.

Topics: Adolescent; Adult; Anemia, Pernicious; Autoantibodies; Autoimmune Diseases; Child; Female; Gastritis; Humans; Intrinsic Factor; Male; Middle Aged; Precancerous Conditions; Stomach; Stomach Neoplasms; Vitamin B 12