Journal of Gastroenterology

, Volume 32, Issue 2, pp 184–188 | Cite as

Helicobacter pylori infection accelerates human gastric mucosal cell proliferation

  • Kazunari Murakami
  • Toshio Fujioka
  • Reiji Kodama
  • Toshihiro Kubota
  • Masashi Tokieda
  • Masaru Nasu
Alimentary Tract


Helicobacter pylori causes chronic atrophic gastritis and intestinal type gastric cancer arises against a background of atrophic gastritis. Increased proliferation of epithelial cells is an important indicator of increased risk for gastric adenocarcinoma. We investigated gastric mucosal cell proliferation inH. pylori-associated gastritis and the effect of eradication therapy on this proliferation in 45 patients endoscopically diagnosed (31 with persistent eradication and 14 in whomH. pylori) recurred.H. pylori status was determined by culture and histology in biopsied specimens from the gastric antrum and corpus. Eradication of the infection was defined as reversal to negative on both tests. In vitro Ki-67 immunostaining of endoscopic biopsy specimens was used to measure mucosal cell proliferation inH. pylori-associated gastritis before and after therapy. The proliferative zone was defined as the distance of Ki-67-positive gastric epithelial cells between the highest and the lowest cells. In patients in whomH. pylori was eradicated, cell proliferation in both the antral and corpus mucosa had decreased 4 weeks after completion of the eradication therapy (P<0.01,P<0.001), and 6 months later, it had markedly decreased (P<0.05,P<0.05) and returned to normal. In patients in whomH. pylori recurred, only antral epithelial cell proliferation was reduced 4 weeks after eradication therapy, but whenH. pylori recurred, determined by culture and histology, cell proliferation level was the same as that before eradication. These results suggest thatH. pylori infection accelerates cell proliferation in gastric mucosa and may play a causal role in the chain of events leading to gastric carcinoma.

Key words

Helicobacter pylori gastric cancer cell proliferation Ki-67 eradication therapy 


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  1. 1.
    Blaser MJ.Helicobacter pylori and the pathogenesis of gastroduodenal i inflammation. J Infect Dis 1990;161:626–633.PubMedGoogle Scholar
  2. 2.
    Wyatt JI.Campylobacter pylori, duodenitis and duodenal ulceration. In: Rathbone BJ, Heatley RV (eds)Campylobacter pylori and gastroduodenal disease. Oxford: Blackwell Scientific, 1989:117–124.Google Scholar
  3. 3.
    Talley NJ, Zinsmeister AR, Weaver A, et al. Gastric adenocarcinoma andHelicobacter pylori infection. J Natl Cancer Inst 1991;83:1734–1739.PubMedCrossRefGoogle Scholar
  4. 4.
    Correa P. The gastric precancerous process. Cancer Surv 1983;2:437–450.Google Scholar
  5. 5.
    Hart-Hansen O, Johansen A, Larsen JK, et al. Cell proliferation in normal and diseased gastric mucosa: Autoradiography after in vitro continuous labelling with titrated thymidine. Acta Pathol Microbiol Scand A 1979;87:217–222.Google Scholar
  6. 6.
    Sipponen P, Kekkei M, Haapakoshi J, et al. Gastric cancer risk in chronic atrophic gastritis: Statistical calculations of cross-sectional data. Int J Cancer 1985;35:173–177PubMedCrossRefGoogle Scholar
  7. 7.
    Ohyama S, Yonemura Y, Miyazaki I. Proliferative activity and malignancy in human gastric cancers. Significance of the proliferation rate and its clinical applications. Cancer 1992;69:314–321.PubMedCrossRefGoogle Scholar
  8. 8.
    Deinlein E, Schmidt H, Riemann JF, et al. DNA flow cytometric measurements in inflammatory and malignant human gastric lesions. Virchows Arch A Pathol Anat Histopathol 1983;402:185–193.PubMedCrossRefGoogle Scholar
  9. 9.
    Hansen OH, Pedersen T, Larsen JK, et al. A method to study cell proliferation kinetics in human gastric mucosa. Gut 1975;16:23–27.PubMedCrossRefGoogle Scholar
  10. 10.
    Weiss LM, Strickler JG, Medeiros LJ, et al. Proliferative rates of non-Hodgkin's lymphomas as assessed by Ki-67 antibody. Hum Pathol 1987;18:1155–1159.PubMedCrossRefGoogle Scholar
  11. 11.
    Shuto R, Fujioka T, Kubota T, et al. Experimental gastritis induced byHelicobacter pylori in Japanese monkeys. Infect Immun 1993;61:933–939.PubMedGoogle Scholar
  12. 12.
    Sasaki K, Matsumura K, Tsuji T, et al. Relationship between labeling indices of Ki-67 and BrdUrd in human malignant tumors. Cancer 1988;62:989–993.PubMedCrossRefGoogle Scholar
  13. 13.
    Raus EAJ, Langenberg W, Houthoff HJ, et al.Campylobacter pyloridis-associated chronic active gastritis. A prospective study of its prevalence and effects of antibacterial and antiulcer treatment. Gastroenterology 1988;94:33–40.Google Scholar
  14. 14.
    Gerdes J, Lemke H, Baisch H, et al. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 1983;133:1710–1715.Google Scholar
  15. 15.
    The Eurogast Study Group. An international association betweenHelicobacter pylori infection and gastric cancer. Lancet 1993; 341:1359–1362.CrossRefGoogle Scholar
  16. 16.
    Lott M, Wright NA Epithelial kinetics control, and consequences of alterations in disease. In: Whitehead R (ed) Gastrointestinal and oesophageal pathology, 1st ed. Edinburgh: Churchill Livingstone, 1992:93–105.Google Scholar
  17. 17.
    Lynch DAF, Mapstone NP, Clarke AMT, et al. Cell proliferation in the gastric corpus inHelicobacter pylori-associated gastritis and after gastric resection. Gut 1995;36:351–353.PubMedCrossRefGoogle Scholar
  18. 18.
    Lynch DAF, Mapstone NP, Clarke AMT, et al. Cell proliferation inHelicobacter pylori-associated gastritis and the effect of eradication therapy. Gut 1995;36:346–350.PubMedCrossRefGoogle Scholar
  19. 19.
    Ken WC, Simmy B, John ADO, et al.Helicobacter pylori infection does not increase gastric antrum mucosal cell proliferation. Am J Gastroenterol 1995;90:64–66.Google Scholar
  20. 20.
    Fan XG, Kelleher D, Fan XJ, et al.Helicobacter pylori increases proliferation of gastric epithelial cells. Gut 1996;38:19–22.PubMedCrossRefGoogle Scholar
  21. 21.
    Prosperi MT, Ferbus D, Karczinski I, et al. A human cDNA corresponding to a gene overexpressed during cell proliferation encodes a product sharing homology with amoebic and bacterial proteins. J Biol Chem 1993;268:11050–11056.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • Kazunari Murakami
    • 1
  • Toshio Fujioka
    • 1
  • Reiji Kodama
    • 1
  • Toshihiro Kubota
    • 1
  • Masashi Tokieda
    • 1
  • Masaru Nasu
    • 1
  1. 1.Second Department of Internal MedicineOita Medical UniversityOitaJapan

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