Irrespective of its etiology, long-standing, non-self-limiting gastric inflammation (mostly in Helicobacter pylori-associated cases) is the cancerization ground on which epidemic (intestinal-type) gastric carcinoma (GC) can develop. The natural history of invasive gastric adenocarcinoma encompasses gastritis, atrophic mucosal changes, and intraepithelial neoplasia (IEN). The topography, the extent and the severity of the atrophic changes significantly correlate with the risk of developing both IEN and GC. In recent years, both noninvasive (serological) tests and invasive (endoscopy/biopsy) procedures have been proposed to stratify patients according to different classes of GC risk. As a consequence, different patient-tailored GC secondary prevention strategies have been put forward. This review summarizes the histological features of H. pylori-related gastritis and the natural history of the disease. Histological and serological strategies to assess GC risk as well as the clinical management of atrophic gastritis patients are also discussed.

1.
Calvet X, Ramírez Lázaro MJ, Lehours P, et al: Diagnosis and epidemiology of Helicobacter pylori infection. Helicobacter 2013;18(suppl 1):5-11.
2.
Brown LM: Helicobacter pylori: epidemiology and routes of transmission. Epidemiol Rev 2000;22:283-297.
3.
Correa P: The biological model of gastric carcinogenesis. IARC Sci Publ 2004;157:301-310.
4.
Rugge M, Capelle LG, Cappellesso R, et al: Precancerous lesions in the stomach: from biology to clinical patient management. Best Pract Res Clin Gastroenterol 2013;27:205-223.
5.
Rugge M, Fassan M, Graham DY: Clinical guidelines: secondary prevention of gastric cancer. Nat Rev Gastroenterol Hepatol 2012;9:128-129.
6.
Owen DA: Stomach; in Mills SE (ed): Histology for Pathologists, ed 3. Philadelphia, Lippincott Williams & Wilkins, 2007, pp 589-602.
7.
Khurana S, Mills JC: The gastric mucosa development and differentiation. Prog Mol Biol Transl Sci 2010;96:93-115.
8.
Jass JR, Filipe MI: The mucin profiles of normal gastric mucosa, intestinal metaplasia and its variants and gastric carcinoma. Histochem J 1981;13:9231-9239.
9.
Chu S, Schubert ML: Gastric secretion. Curr Opin Gastroenterol 2012;28:587-593.
10.
Qiao XT, Gumucio DL: Current molecular markers for gastric progenitor cells and gastric cancer stem cells. J Gastroenterol 2011;46:855-865.
11.
Han ME, Oh SO: Gastric stem cells and gastric cancer stem cells. Anat Cell Biol 2013;46:8-18.
12.
Miller ML, Andringa A, Zavros Y, et al: Volume density, distribution, and ultrastructure of secretory and basolateral membranes and mitochondria predict parietal cell secretory (dys)function. J Biomed Biotechnol 2010;2010:394198.
13.
Madsen KM, Tisher CC: Structure-function relationships in H+-secreting epithelia. Fed Proc 1985;44:2704-2709.
14.
Gritti I, Banfi G, Roi GS: Pepsinogens: physiology, pharmacology pathophysiology and exercise. Pharmacol Res 2000;41:265-281.
15.
Samloff IM: Cellular localization of group I pepsinogens in human gastric mucosa by immunofluorescence. Gastroenterology 1971;61:185-188.
16.
Samloff IM, Liebman WM: Cellular localization of the group II pepsinogens in human stomach and duodenum by immunofluorescence. Gastroenterology 1973;65:36-42.
17.
Rugge M, Genta RM: Staging and grading of chronic gastritis. Hum Pathol 2005;36:228-233.
18.
Rugge M, Pennelli G, Pilozzi E, et al: Gastritis: the histology report. Dig Liver Dis 2011;43(suppl 4):S373-S384.
19.
Ferreri AJ, Govi S, Ponzoni M: Marginal zone lymphomas and infectious agents. Semin Cancer Biol 2013;23:431-440.
20.
Wu TT, Hamilton SR: Lymphocytic gastritis: association with etiology and topology. Am J Surg Pathol 1999;23:153-158.
21.
Kimura K, Satoh K, Ido K, et al: Gastritis in the Japanese stomach. Scand J Gastroenterol Suppl 1996;214:17-20.
22.
Correa P, Piazuelo MB: Natural history of Helicobacter pylori infection. Dig Liver Dis 2008;40:490-496.
23.
Uemura N, Okamoto S, Yamamoto S: Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 2001;345:784-789.
24.
Rugge M, Correa P, Dixon MF, et al: Gastric mucosal atrophy: interobserver consistency using new criteria for classification and grading. Aliment Pharmacol Ther 2002;16:1249-1259.
25.
Ruiz B, Garay J, Correa P, et al: Morphometric evaluation of gastric antral atrophy: improvement after cure of Helicobacter pylori infection. Am J Gastroenterol 2001;96:3281-3287.
26.
Rugge M, Meggio A, Pennelli G, et al: Gastritis staging in clinical practice: the OLGA staging system. Gut 2007;56:631-636.
27.
Genta RM: Differential diagnosis of reactive gastropathy. Semin Diagn Pathol 2005;22:273-283.
28.
Weis VG, Goldenring JR: Current understanding of SPEM and its standing in the preneoplastic process. Gastric Cancer 2009;12:189-197.
29.
Nam KT, Lee HJ, Sousa JF, et al: Mature chief cells are cryptic progenitors for metaplasia in the stomach. Gastroenterology 2010;139:2028-2037.
30.
Correa P, Piazuelo MB, Wilson KT: Pathology of gastric intestinal metaplasia: clinical implications. Am J Gastroenterol 2010;105:493-498.
31.
Matsukura N, Suzuki K, Kawachi T, et al: Distribution of marker enzymes and mucin in intestinal metaplasia in human stomach and relation to complete and incomplete types of intestinal metaplasia to minute gastric carcinomas. J Natl Cancer Inst 1980;65:231-240.
32.
Filipe MI, Munoz N, Matko I, et al: Intestinal metaplasia types and the risk of gastric cancer: a cohort study in Slovenia. Int J Cancer 1994;57:324-329.
33.
Jass JR, Filipe MI: Sulphomucins and precancerous lesions of the human stomach. Histopathology 1980;4:271-279.
34.
LeungWK, Sung JJY: Intestinal metaplasia and gastric carcinogenesis. Aliment Pharmacol Ther 2002;16:1209-1216.
35.
Gutierrez-Gonzalez L, Wright NA: Biology of intestinal metaplasia in 2008: more than a simple phenotypic alteration. Dig Liver Dis 2008;40:510-522.
36.
Silva E, Teixeira A, David L, et al: Mucins as key molecules for the classification of intestinal metaplasia of the stomach. Virchows Arch 2002;440:311-317.
37.
Piazuelo MB, Haque S, Delgado A, et al: Phenotypic differences between esophageal and gastric intestinal metaplasia. Mod Pathol 2004;17:62-74.
38.
Vannella L, Lahner E, Osborn J, et al: Risk factors for progression to gastric neoplastic lesions in patients with atrophic gastritis. Aliment Pharmacol Ther 2010;31:1042-1050.
39.
Morson BC, Sobin LH, Grundmann E, et al: Precancerous conditions and epithelial dysplasia in the stomach. J Clin Pathol 1980;33:711-721.
40.
Lauwers GY, Riddell RH: Gastric epithelial dysplasia. Gut 1999;45:784-790.
41.
Bosman FT, Carneiro F, Hruban RH, Theise ND (eds): WHO Classification of Tumours of the Digestive System. Lyon, International Agency for Research on Cancer, 2010.
42.
Rugge M, Correa P, Dixon MF, et al: Gastric dysplasia: the Padova international classification. Am J Surg Pathol 2000;24:167-176.
43.
Schlemper RJ, Riddell RH, Kato Y, et al: The Vienna classification of gastrointestinal epithelial neoplasia. Gut 2000;47:251-255.
44.
Fassan M, Pizzi M, Farinati F, et al: Lesions indefinite for intraepithelial neoplasia and OLGA staging for gastric atrophy. Am J Clin Pathol 2012;137:727-732.
45.
Miehlke S, Hackelsberger A, Meining A, et al: Severe expression of corpus gastritis is characteristic in gastric cancer patients infected with Helicobacter pylori. Br J Cancer 1998;78:263-266.
46.
Cassaro M, Rugge M, Gutierrez O, et al: Topographic patterns of intestinal metaplasia and gastric cancer. Am J Gastroenterol 2000;95:1431-1438.
47.
Genta RM, Rugge M: Assessing risks for gastric cancer: new tools for pathologists. World J Gastroenterol 2006;12:5622-5627.
48.
Rugge M, Genta RM, OLGA-Group: Staging gastritis: an international proposal. Gastroenterology 2005;129:1807-1808.
49.
Dixon MF, Genta RM, Yardley JH, et al: Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol 1996;20:1161-1181.
50.
Rugge M, Correa P, Di Mario F, et al: OLGA staging for gastritis: a tutorial. Dig Liver Dis 2008;40:650-658.
51.
Kodama M, Murakami K, Okimoto T, et al: Histological characteristics of gastric mucosa prior to Helicobacter pylori eradication may predict gastric cancer. Scand J Gastroenterol 2013;48:1249-1256.
52.
Rugge M, de Boni M, Pennelli G, et al: Gastritis OLGA-staging and gastric cancer risk: a twelve-year clinico-pathological follow-up study. Aliment Pharmacol Ther 2010;31:1104-1111.
53.
Rugge M, Kim JG, Mahachai V, et al: OLGA gastritis staging in young adults and country-specific gastric cancer risk. Int J Surg Pathol 2008;16:150-154.
54.
Rugge M, Fassan M, Pizzi M, et al: Operative Link for Gastritis Assessment gastritis staging incorporates intestinal metaplasia subtyping. Hum Pathol 2011;42:1539-1544.
55.
Capelle LG, de Vries AC, Haringsma J, et al: The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc 2010;71:1150-1158.
56.
Rugge M, Fassan M, Pizzi M, et al: Operative link for gastritis assessment vs operative link on intestinal metaplasia assessment. World J Gastroenterol 2011;17:4596-4601.
57.
Agréus L, Kuipers EJ, Kupcinskas L, et al: Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers. Scand J Gastroenterol 2012;47:136-147.
58.
Miki K, Fujishiro M, Kodashima S, et al: Long-term results of gastric cancer screening using the serum pepsinogen test method among an asymptomatic middle-aged Japanese population. Dig Endosc 2009;21:78-81.
59.
Sipponen P, Ranta P, Helske T, et al: Serum levels of amidated gastrin-17 and pepsinogen I in atrophic gastritis: an observational case-control study. Scand J Gastroenterol 2002;37:785-791.
60.
Kikuchi R, Abe Y, Iijima K, et al: Low serum levels of pepsinogen and gastrin 17 are predictive of extensive gastric atrophy with high-risk of early gastric cancer. Tohoku J Exp Med 2011;223:35-44.
61.
Väänänen H, Vauhkonen M, Helske T, et al: Non-endoscopic diagnosis of atrophic gastritis with a blood test. Correlation between gastric histology and serum levels of gastrin-17 and pepsinogen I: a multicentre study. Eur J Gastroenterol Hepatol 2003;15:885-891.
62.
Storskrubb T, Aro P, Ronkainen J, Sipponen P, et al: Serum biomarkers provide an accurate method for diagnosis of atrophic gastritis in a general population: the Kalixanda study. Scand J Gastroenterol 2008;43:1448-1455.
63.
Di Mario F, Cavallaro LG, Moussa AM, et al: Usefulness of serum pepsinogens in Helicobacter pylori chronic gastritis: relationship with inflammation, activity, and density of the bacterium. Dig Dis Sci 2006;51:1791-1795.
64.
de Martel C, Forman D, Plummer M: Gastric cancer: epidemiology and risk factors. Gastroenterol Clin North Am 2013;42:219-240.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.