Immunolocalization of transforming growth factor-α in normal and diseased human gastric mucosa

Abstract

Roles for transforming growth factor—α (TGFα) in the stomach include cell migration and proliferation, inhibition of acid secretion, and cytoprotection. The authors have previously shown increased TGFα expression in rat gastric mucosa in response to acute gastric injury. They also have shown that TGFα immunoreactivity is increased in the gastric mucosa of four patients with Ménétrier's disease. To further characterize TGFα immunoreactivity in human gastric mucosa, the authors have performed immunohistochemical analysis with an anti-TGFα monoclonal antibody on human gastric biopsies ( n = 25) showing either normal ( n = 8), mild reactive/ reparative change in common conditions with or without associated gastritis ( n = 13), and exaggerated mucosal change in proliferative conditions (Ménétrier's disease, hypertrophic lymphocytic gastritis, and hyperplastic polyps) ( n = 17). All normal biopsies showed a predictable pattern of TGFα immunostaining, with significant positivity found only in foveolar cells at the luminal surface and parietal cells, sparing foveolar cells in the gastric pits, mucous neck cells and chief cells of the gastric glands. Three patients with mild foveolar hyperplasia without associated inflammation did not deviate from the normal pattern except in foci of reactive epithelial change. Ten of 11 patients with chronic active gastritis, in addition to this normal staining pattern, demonstrated significant immunoreactivity in deeper foveolar cells and mucous neck cells showing reactive epithelial changes, defined as the presence of nuclear enlargement and nucleolar prominence with or without mucin depletion. Three cases of ulceration with associated reactive epithelial changes also showed increased immunoreactivity. Furthermore, five cases of Ménétrier's disease with massive foveolar hyperplasia and minimal inflammation (MFH) and six cases with hypertrophic lymphocytic gastritis (HLG) have been studied, and both show full-thickness TGFα immunoreactivity restricted to the gastric epithelium. This pattern of staining is indistinguishable from that observed in two cases of hyperplastic polyps but differs significantly from that observed in cases of mild foveolar hyperplasia. These results further define patterns of TGFα immunostaining in normal, reactive/reparative and exaggerated proliferative human gastric biopsies, confirm participation of TGFα in the response to gastric mucosal injury, and provide additional support for a possible role for TGFα in the pathogenesis of proliferative gastric disorders including Ménétrier's disease, hypertrophic lymphocytic gastritis, and hyperplastic gastric polyps.