title: Atrophy-metaplasia-dysplasia-carcinoma sequence in the stomach: a reality or merely an hypothesis?
abstract: The results of recent investigations have suggested that the old hypothesis of an atrophy-metaplasia-dysplasia-carcinoma sequence in the stomach needs to be qualified. The most common cause of intestinal metaplasia is Helicobacter pylori gastritis. The consequence of this intestinal metaplasia is focal atrophy. Helicobacter pylori infection may also trigger an autoimmune gastritis of the corpus mucosa, with atrophy and intestinal metaplasia. Most intestinal metaplasias are only 'paracancerous' but not 'precancerous' lesions. Diffuse gastric carcinomas, such as the signet ring cell carcinoma, arise independently of intestinal metaplasia. Histogenetically, numerous carcinomas of the stomach are primarily of the gastric type, and may secondarily change into the intestinal type.High-grade intra-epithelial neoplasias (dysplasias) detected during the biopsy-based diagnostic work-up appear to be a marker for carcinoma and must, therefore, be removed endoscopically. The detection of intestinal metaplasia in routinely obtained biopsy material is subject to sampling error and is, therefore, not a suitable marker for an increased risk of a gastric carcinoma developing. As an alternative, the concept of gastritis of the carcinoma phenotype, which is more frequently found in early gastric carcinomas and in the relatives of gastric carcinoma patients, has been developed. In this concept, the diffuse parameters of grade and activity of the gastritis in the antrum and corpus, which are independent of sampling error, are subjected to a comparative analysis. A risk gastritis of the carcinoma phenotype is diagnosed when the grade and activity of the gastritis in the corpus are at least equally as pronounced as in the antrum. Currently, this concept is being tested in a prospective ongoing study. Future studies must show whether, and if so which, immunohistochemical or molecular-genetically detectable changes can be applied as risk markers in the diagnostic work-up. Helicobacter pylori eradication probably does not lead to complete regression of the intestinal metaplasia and ensuing focal atrophy. However, eradication of H. pylori does lead to the normalization of changes that can lead to mutations of the stem cells of the gastric mucosa (free radicals, nitric oxide, cell proliferation and vitamin C secretion).
authors.affiliation: Medizinische Klinik II, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675 München, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Meining
authors.forename: A
authors.initials: A
authors.lastname: Morgner
authors.forename: S
authors.initials: S
authors.lastname: Miehlke
authors.forename: E
authors.initials: E
authors.lastname: Bayerdörffer
authors.forename: M
authors.initials: M
authors.lastname: Stolte
mesh_terms: D005753:Gastric Mucosa / Q000473:pathology*; D005757:Gastritis, Atrophic / Q000150:complications*; D017491:Genes, APC; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D008679:Metaplasia / Q000150:complications* / Q000382:microbiology; D009077:Mucins / Q000096:biosynthesis; D011230:Precancerous Conditions / Q000209:etiology*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D009077:Mucins