Skip to main content

Proliferative activity of gastric epithelium in progressive stages ofHelicobacter pylori infection

Digestive Diseases and Sciences volume 41, pages 1132–1138 (1996)Cite this article

Abstract

Helicobacter pylori (HP) infection is the main etiopathogenetic agent responsible for inflammatory and ulcerative changes in gastroduodenal mucosa and the basis for both intestinal and diffuse types of gastric carcinoma. In this latter case, intestinal metaplasia is the intermediary between gastritis and cancer. In this study we describe the proliferative activity of gastric epithelium in the progressive stages of HP infection. The expression of proliferating cell nuclear antigen (PCNA), which has proven to be a reliable method for this evaluation, was used as a marker. The study was performed on endoscopic biopsies of the gastric antrum of 40 patients, who were divided into five groups, eight in each group: normal histology and endoscopy, HP−; histological HP+ gastritis with normal endoscopy; histological HP+ gastritis with endoscopic evidence of chronic erosions; complete and incomplete intestinal metaplasia in a HP+ stomach. PCNA was detected by immunohistochemistry and expressed as labeling index, ie, percentage of positive nuclei either in the whole or upper third of foveolae. Our data show a progressive increase of epithelial proliferation in the successive stages of HP infection ranging from gastritis alone to the development of incomplete intestinal metaplasia, a well-known precancerous condition. The proliferative pattern tended to expand towards the upper foveolar third, which in normal conditions does not represent a site of epithelial renewal. These alterations may be related to the development of neoplastic transformations of gastric epithelium. It is well known that genetic mutations are facilitated in proliferating cells. Therefore, our results indicate that the high epithelial turnover, expressed by PCNA LI, may be an indicator of increased risk of neoplastic changes in long-standing untreated HP+ chronic gastritis.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. MacDonald WC, Trier JS, Everett NB: Cell proliferation and migration in stomach, duodenum and rectum of man. Gastroenterology 46:405–417, 1964

    Google Scholar 

  2. Allen A, Flemstrom G, Garner A, Kivilaakso E: Gastroduodenal mucosal protection. Physiol Rev 73(4):823–857, 1993

    Google Scholar 

  3. Morson BC, Sobin LH, Grundmann E, Johansen A, Nagayo T, Serck-Hansen A: Precancerous conditions and epithelial dysplasia in the stomach. J Clin Pathol 33:711–721, 1980

    Google Scholar 

  4. Paull G, Yardley JH: Pathology ofC. pylori associated gastric and esophageal lesions.In Campylobacter pylori in Gastritis and Peptic Ulcer Disease. MI Blaser (ed). Igaku-Shoin, New York, 1989

    Google Scholar 

  5. Sipponen P: Long-term consequences of gastroduodenal inflammation. Eur J Gastroenterol Hepatol 4(2S):25–29, 1992

    Google Scholar 

  6. Correa P: Is gastric carcinoma an infectious disease? N Engl J Med 325:1170–1171, 1991

    Google Scholar 

  7. Sobala GM, Pignatelli B, Schorah CI, Bartsch II, Sanderson M, Dixon MF, Shires S, King RF, Axon ATR: Levels of nitrite, nitrate,N-nitroso compounds, ascorbic and total bile acids in gastric juice of patients with and without precancerous conditions of the stomach. Carcinogenesis 12:193–198, 1991

    Google Scholar 

  8. Ierardi E, Monno RA, Ingrosso M, Panza P, DeLorenzis A, Rissi S, Pisani A, Valenza N, Francavilla A: Identification of a subgroup at high risk for gastric cancer in patients with chronic gastritis andHelicobacter pylori. Ir J Med Sci 161(2):70, 1992

    Google Scholar 

  9. Celis JE, Celis A: Cell cycle dependent variations in the distribution of the nuclear protein cyclin proliferating cell nuclear antigen in cultured cells. Proc Natl Acad Sci USA Vol. 82:3262–3266, 1985

    Google Scholar 

  10. Kamel OW, LeBrun DP, Davis RE, Gerald JB, Wurnke RA: Growth fraction extination of malignant lymphomas in formalin fixed paraffin embedded tissue using anti-PCNA/cyclin 19A2. Am J Pathol 138:1471–1477, 1991

    Google Scholar 

  11. Sarraf CE, McCornick CSF, Brown GR, Price YE, Hall PA, Lane DP, Alison MR: Proliferating cell nuclear antigen immunolocalization in gastrointestinal epithelia. Digestion 50:85–91, 1991

    Google Scholar 

  12. Yamada K, Yoshitaka K, Sato M, Auhnem DJ: Proliferating cell nuclear antigen in normal, preneoplastic and neoplastic colonic epithelium in the rat. Gastroenterology 103:160–167, 1992

    Google Scholar 

  13. Francavilla A, Ierardi E, Barone M, DeLorenzis A, Coppolecchia P: Evaluation of cell proliferationin vivo andin vitro in the epithelium of gastrointestinal tract: A comparison of different techniques. Proceedings of II United Gastroenterology Week, Barcelona, Spain, July 19–24, 1993, A131

  14. Filipe MI, Mendes R, Lane DP, Morris RW: Assessment of proliferating cell nuclear antigen expression in precursor stages of gastric carcinoma using the PC10 antibody to PCNA. Histopathology 22:349–354, 1993

    Google Scholar 

  15. Sokal RR, Rohlf FJ: Biometry, San Francisco, WH Freeman, 1969, p 247

    Google Scholar 

  16. Lorenz J, Gyenes E, Ruth GH, Borsch G: Endoscopic diagnosis ofHelicobacter pylori gastritis. Gastroenterology 104:A126, 1993

  17. Jass JR: Role of intestinal metaplasia in the histogenesis of gastric carcinoma. J Clin Pathol 33(9):801–810, 1980

    Google Scholar 

  18. Jass JR, Filipe MI: A variant of intestinal metaplasia associated with gastric carcinoma: A histochemical study. Histopathology 3:191–199, 1979

    Google Scholar 

  19. Rokkas T, Filipe MI, Sladen GE: Detection of an increased incidence of early gastric cancer in patients with intestinal metaplasia type III who followed up. Gut 31:1110–1113, 1991

    Google Scholar 

  20. Morson BC: Carcinoma arising from areas of intestinal metaplasia in the gastric mucosa. Br J Cancer 9:377–385, 1955

    Google Scholar 

  21. Morson BC: Precancerous lesions of upper gastrointestinal tract. JAMA 179:311–315, 1962

    Google Scholar 

  22. Brenes F, Ruiz B, Correa P, Hunter F, Rhamakrishnan T, Fontham E, Tei-Ying Shi:Helicobacter pylori causes hyperproliferation of the gastric epithelium: Pre- and posteradication indices of proliferating cell nuclear antigen. Am J Gastroenterol 88:1870–1875, 1993

    Google Scholar 

  23. Fraser AG, Sim R, Sankey EA, Dillon AP, Pounder RE: Effect of eradication ofHelicobacter pylori on gastric epithelial cell proliferation. Aliment Pharmacol Ther 8(2):167–173, 1994

    Google Scholar 

  24. Ames BN, Gold LS: Too many rodent carcinogens: Mitogenesis increases mutagenesis. Science 249:970–971, 1990

    Google Scholar 

  25. Fox JG: Gastric disease in ferrets: Effect ofHelicobacter mustelae, nitrosamines and reconstructive gastric surgery. Eur J Gastroenterol Hepatol 6(1S):57–65, 1994

    Google Scholar 

  26. Fraser P, Chilvers C, Beral V, Hill MJ: Nitrate and human cancer: A review of the evidence. Int J Epidemiol 9:3–11, 1980

    Google Scholar 

  27. Correa P, Cuello C, Fajardo LF, Haenszel W, Bolanos O, De Ramirez B: Diet and gastric cancer: Nutrition survey in a high risk area. J Natl Cancer Inst 70:673–678, 1983

    Google Scholar 

  28. Chen VW, Abu-Elyazeed RR, Zavala DE, Ktsanes VK, Haenszel W, Cuello C, Montos G, Correa P: Risk factors of gastric precancerous lesions in a high risk Columbion population: Nitrate and nitrite. I Salt. Nutr Cancer 13:59–65, 1990

    Google Scholar 

  29. Iwanaga T, Han H, Adachi K, Fujita T: A novel mechanism for disposing of effect on epithelial cells in the small intestine of guinea pigs. Gastroenterology 105:1089–1097, 1993

    Google Scholar 

  30. Croitoru K, Riddell RII: Reduce, reuse and recycle: Shedding light on shedding cells. Gastroenterology 105:1243–1250, 1993

    Google Scholar 

  31. Vujanovic NL, Polimeno L, Francavilla A, Chambers WH, Starzl TE, Heberman RB, Whiteside T: Changes of liver-resident natural killer cells during liver regeneration in rats. J Immunol (in press)

Download references

Author information

Affiliations

  1. From the Department of Gastroenterology, Clinica Medica I, Università degli Studi di Bari, 70124, Bari, Italy

    C. Panella MD, E. Ierardi MD, L. Polimeno PhD, T. Balzano MD, M. Ingrosso MD, A. Amoruso MD, A. Traversa MD &  A. Francavilla MD, PhD

  2. Department of Surgery, School of Medicine, University of Pittsburgh, 16234, Pittsburgh, Pennsylvania

    C. Panella MD, E. Ierardi MD, L. Polimeno PhD, T. Balzano MD, M. Ingrosso MD, A. Amoruso MD, A. Traversa MD &  A. Francavilla MD, PhD

Authors
  1. C. Panella MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Ierardi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Polimeno PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T. Balzano MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Ingrosso MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Amoruso MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Traversa MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A. Francavilla MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This work was supported by the Consiglio Nazionale delle Ricerche ACRO Program grant 94.01132 PF 39.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Panella, C., Ierardi, E., Polimeno, L. et al. Proliferative activity of gastric epithelium in progressive stages ofHelicobacter pylori infection. Digest Dis Sci 41, 1132–1138 (1996). https://doi.org/10.1007/BF02088228

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02088228

Key words

  • Helicobacter pylori
  • proliferating cell nuclear antigen
  • chronic gastritis
  • intestinal metaplasia