Helicobacter pylori-induced hyperproliferation: Relevance for gastric cancer development in connection with mutagenic factors

Aims. Current data on Helicobacter pylori induced regenerative hyperprolife ration of the antral gastric mucosa and significance in cancer development are still under discussion and investigation. An improved method for evalua tion of the regeneratory process in antral mucosa is introduced and compare d with the conventional method used for determination of proliferating cell s in perpendicular sections of the gastric mucosa. Methods. Using a combina tion of immunohistochemistry and PAS-staining the expression of Ki-67 (MiB1 )-proliferation associated antigen was analyzed in 50 Helicobacter pylori ( Hp) positive and 35 negative biopsies of the gastric antrum. PAS-staining w as performed to identify the proliferative zone of the antral gastric gland s The degree of inflammation was evaluated by grades on routinely H & E-sta ined slides. Results. Proliferative activity is significantly increased in Hp-positive cases (p=0.00095) compared to negative ones: By using the conve ntionally applied proliferation index, every nucleus has to be counted and the proliferation zone is identified by at least one positive stained nucle us. The method presented here seems to be easier because the proliferative zone is clearly identified by PAS staining of neutral glycoproteins charact eristic far the proliferation zone of antral glands. The density of labeled nuclei is determined and is expressed as a proliferation factor: This fact or gives more distinct values, is easier to evaluate and shows a better cor relation with the helicobacter status and the dea ee of inflammation. These results are discussed in relation to the data fi om the literature and wit h a view to other relevant factors in the course of carcinogenesis such as growth factors, mainly EGF, p53 mutation and role of apoptosis, genetic ins tability and local production of oxidants. Conclusion. Helicobacter pylori induces an increase of regenerative proliferation activity. Under these con ditions the chance of mutation is increased and time for DNA repair reduced . This could be at least a part of multiple step carcinogenesis. The newly introduced combination of staining procedures (PAS/MiBI) allows a more diff erentiated evaluation of the proliferation zone and its widening This metho d can be more easily handled in-follow-up studies than the method using per pendicular sections because in this method heavy irregularities of gland pa ttern induced by accompanying inflammatory processes considerably hinder ev aluation.