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

Aims. Current data on Helicobacter pylori induced regenerative hyperproliferation of the antral gastric mucosa and significance in cancer development are still under discussion and investigation. An improved method for evaluation of the regeneratory process in antral mucosa is introduced and compared with the conventional method used for determination of proliferating cells in perpendicular sections of the gastric mucosa. Methods. Using a combination of immunohisto-chemistry 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 was performed to identify the proliferative zone of the antral gastric glands. The degree of inflammation was evaluated by grades on routinely H & E-stained slides. Results. Proliferative activity is significantly increased in Hp-positive cases (p=0.00095) compared to negative ones: By using the conventionally applied proliferation index, every nucleus has to be counted and the proliferation zone is identified by at least one positive stained nucleus. The method presented here seems to be easier because the proliferative zone is clearly identified by PAS staining of neutral glycoproteins characteristic for the proliferation zone of antral glands. The density of labeled nuclei is determined and is expressed as a proliferation factor. This factor gives more distinct values, is easier to evaluate and shows a better correlation with the helicobacter status and the degree of inflammation. These results are discussed in relation to the data from the literature and with a view to other relevant factors in the course of carcinogenesis, such as growth factors, mainly EGF, p53 mutation and role of apoptosis, genetic instability and local production of oxidants. Conclusion. Helicobacter pylori induces an increase of regenerative proliferation activity. Under these conditions 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 differentiated evaluation of the proliferation zone and its widening. This method can he more easily handled in follow-up studies than the method using perpendicular sections because in this method heavy irregularities of gland pattern induced by accompanying inflammatory processes considerably hinder evaluation.