OBJECTIVE: Why only some patients colonized with Helicobacter pylori (H. pylori) develop atrophy, a preneoplastic change, is not known. Because gastric mucosal mass is dependent upon a balance between epithelial proliferation and turnover, we hypothesized that atrophy may develop due to increased apoptosis relative to proliferation. METHODS: Gastric epithelial apoptosis was measured by terminal deoxyuridine nucleotide nick end labeling (TUNEL) assay and proliferation by Ki-67 immunohistochemistry in gastric corpus biopsies in a unique cohort of patients followed for 31 yr (1952-1983). Sixteen patients who developed atrophy over this time were selected (cases), with two matched controls, who did not develop atrophy, for each. Apoptosis and proliferation were measured in the corpus biopsies taken in 1952. RESULTS: Cases (N = 16) and controls (N = 32) were well matched for age, sex, initial histology, and severity of H. pylori infection. In the initial (1952) biopsies, 4.3 +/- 1.7 cells (mean +/- SEM) per gland were Ki-67-positive in the cases, compared with 2.1 +/- 0.4 in controls (p = 0.48). 9.2 +/- 2.3 cells per gland were terminal deoxyuridine nucleotide nick end labeling-positive in cases, compared with 6.3 +/- 0.8 in controls (p = 0.29). Proliferation to apoptosis ratios were similar in both groups (cases, 0.38 +/- 0.16; controls 0.39 +/- 0.08, p = 0.37). CONCLUSIONS: Patients who later developed atrophy, initially had mildly (but not statistically significant) increased gastric epithelial cell proliferation and apoptosis, compared with those patients who did not develop atrophy, suggesting increased cellular turnover in the atrophy group. However, in these patients with gastritis, the ratio of apoptosis to proliferation was not a determinant of risk for development of atrophy decades later.
OBJECTIVE: Why only some patients colonized with Helicobacter pylori (H. pylori) develop atrophy, a preneoplastic change, is not known. Because gastric mucosal mass is dependent upon a balance between epithelial proliferation and turnover, we hypothesized that atrophy may develop due to increased apoptosis relative to proliferation. METHODS: Gastric epithelial apoptosis was measured by terminal deoxyuridine nucleotide nick end labeling (TUNEL) assay and proliferation by Ki-67 immunohistochemistry in gastric corpus biopsies in a unique cohort of patients followed for 31 yr (1952-1983). Sixteen patients who developed atrophy over this time were selected (cases), with two matched controls, who did not develop atrophy, for each. Apoptosis and proliferation were measured in the corpus biopsies taken in 1952. RESULTS: Cases (N = 16) and controls (N = 32) were well matched for age, sex, initial histology, and severity of H. pyloriinfection. In the initial (1952) biopsies, 4.3 +/- 1.7 cells (mean +/- SEM) per gland were Ki-67-positive in the cases, compared with 2.1 +/- 0.4 in controls (p = 0.48). 9.2 +/- 2.3 cells per gland were terminal deoxyuridine nucleotide nick end labeling-positive in cases, compared with 6.3 +/- 0.8 in controls (p = 0.29). Proliferation to apoptosis ratios were similar in both groups (cases, 0.38 +/- 0.16; controls 0.39 +/- 0.08, p = 0.37). CONCLUSIONS:Patients who later developed atrophy, initially had mildly (but not statistically significant) increased gastric epithelial cell proliferation and apoptosis, compared with those patients who did not develop atrophy, suggesting increased cellular turnover in the atrophy group. However, in these patients with gastritis, the ratio of apoptosis to proliferation was not a determinant of risk for development of atrophy decades later.