Abstract
To assess a role of microsatellite instability (MSI) in the development of gastric adenocarcinoma or adenoma from chronic gastritis, we analysed mutations of five microsatellite loci in gastritis, adenoma and adenocarcinoma retrospectively. Gastric mucosa was biopsied from the same area in each patient at different periods and examined for MSI. Only one of 55 patients with chronic gastritis revealed MSI-H phenotype and the other 54 patients showed microsatellite stable (MSS) phenotypes. In six of 17 patients with gastric adenoma or well-differentiated adenocarcinoma, MSI-positive phenotypes were demonstrated. Interestingly, all of six patients showing MSI, including three high-level MSI (MSI-H) cases and three low-level (MSH-L) cases, had already revealed MSI at the stage of chronic gastritis. In two of three MSI-H cases, the identical MSI patterns had been observed at the stage of gastritis 1.5–7 years before the final diagnosis of adenocarcinoma. The adjacent gastritis mucosa within 10 mm from the carcinoma demonstrated MSI as well. MSI was not found in any of 35 patients with Helicobacter pylori infection, but found in one of 30 patients without infection. Moreover, two of three cases of gastric adenoma or well-differentiated adenocarcinoma with MSI-H at the stage of chronic gastritis showed no evidence of Helicobacter pylori infection throughout the observation periods. These results indicate that MSI in biopsy specimens at the stage of chronic gastritis may predict the risk of the progression to adenoma and well-differentiated adenocarcinoma, and that Helicobacter pylori infection itself may not induce MSI directly in the gastric mucosa. © 2000 Cancer Research Campaign
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Aaltonen LA, Peltomaki P and Leach FS (1993) Clues to the pathogenesis of familial colorectal cancer. Science 260: 812–816
Baik SC, Youn HS and Chung MH (1996) Increased oxidative DNA damage in Helicobacter pylori -infected human gastric mucosa. Cancer Res 56: 1279–1282
Boland CR, Thibodeau SN and Hamilton SR (1998) A national cancer institute workshop on microsatellite instability for cancer deletion and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58: 5248–5257
Bronner CE, Baker SM and Morrison PT (1994) Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 368: 258–261
Buonsanti G, Calistri D and Padovan L (1997) Microsatellite instability in intestinal and diffuse-type gastric carcinoma. J Pathol 182: 167–173
Correa P (1988) Chronic gastritis: a clinico-pathological classification. Am J Gastroenterol 83: 504–509
Correa P (1992) Human gastric carcinogenesis, a multistep and multifactorial process. Cancer Res 52: 6735–6740
Chong J-M, Fukayama M and Hayashi Y (1994) Microsatellite instability in the progression of gastric carcinoma. Cancer 54: 4595–4597
Chung Y-J, Song J-M and Lee J-Y (1996) Microsatellite instability-associated mutations associate preferentially with the intestinal type of primary gastric carcinomas in a high-risk population. Cancer Res 56: 4662–4665
Dos Santos NR, Seruca R and Constancia M (1996) Microsatellite instability at multiple loci in gastric carcinoma; clinicopathologic implications and prognosis. Gastroenterology 110: 38–44
Eshleman JR and Markowitz SD (1995) Microsatellite instability in inherited and sporadic neoplasms. Curr Opin Oncol 7: 83–89
Goodwin CS and Mendall MM (1997) Helicobacter pylori infection. Lancet 349: 265–269
Han H-J, Yanagisawa A and Kato Y (1993) Genetic instability in pancreatic cancer and poorly differentiated type of gastric cancer. Cancer Res 53: 5087–5089
Ionov Y, Peinado MA and Malkhosyan S (1993) Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 363: 558–561
Kim JJ, Baek MJ and Kim L (1999) Accumulated frameshift mutations at coding nucleotide repeats during the progression of gastric carcinoma with microsatellite instability. Lab Invest 79: 1113–1120
Leach FS, Nicolaides NC and Papadopoulos N (1993) Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75: 1215–1225
Nomura A, Stemmermann GN and Chyou P (1991) Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med 325: 1132–1136
Parsonnet J, Friedman GD and Vandersteen DP (1991) Helocobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 325: 1127–1131
Parsons R, Li G-M and Longley MJ (1993) Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell 75: 1227–1236
Rugee M, Farinati F and Baffa R (1994) Gastric epithelial dysplasia in the natural history of gastric cancer: a multicenter prospective follow-up study. Gastroenterology 107: 1288–1296
Sano T, Kobori O and Muto T (1992) Lymph node metastasis from early gastric cancer: endoscopic resection of tumour. Br J Surg 79: 241–244
Schlemper RJ, Itabashi M and Kato Y (1997) Differences in diagnostic criteria for gastric carcinoma between Japanese and Western pathologists. Lancet 349: 1725–1729
Semba S, Yokozaki H and Yamamoto S (1996) Microsatellite instability in precancerous lesions and adenocarcinomas of the stomach. Cancer 77: 1620–1627
Sipponen P, Kekki M and Siurala M (1984) Age-related trends of gastritis and intestinal metaplasia in gastric carcinoma patients and in controls representing the population at large. Br J Cancer 49: 521–530
Tamura G, Sakata K and Maesawa C (1995) Microsatellite alterations in adenoma and differentiated adenocarcinoma of the stomach. Cancer Res 55: 1933–1936
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Kashiwagi, K., Watanabe, M., Ezaki, T. et al. Clinical usefulness of microsatellite instability for the prediction of gastric adenoma or adenocarcinoma in patients with chronic gastritis. Br J Cancer 82, 1814–1818 (2000). https://doi.org/10.1054/bjoc.1999.1154
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1054/bjoc.1999.1154
Keywords
This article is cited by
-
The immune microenvironment in gastric adenocarcinoma
Nature Reviews Gastroenterology & Hepatology (2022)
-
Helicobacter, Inflammation, and Gastric Cancer
Current Pathobiology Reports (2013)
-
Premalignant lesions in gastric cancer
Clinical Journal of Gastroenterology (2010)