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Epidermal growth factor receptor (EGFR) and its ligands play a pivotal role in normal cell proliferation, tissue repair, and ulcer healing. Ligand-induced activation of EGFR inhibits acid secretion, protect gastric mucosa against injury, mediates mucosal adaptation, and accelerates gastroduodenal ulcer healing. However, the cellular events that regulate EGFR in gastric ulcer have not been fully elucidated. Recently, a novel negative regulator of EGFR, referred to as ERRP (EGFR Related Protein) has been identified. The aim of this study was to investigate expression and localization of ERRP in gastric ulcer tissues and to examine a possible role of ERRP in ulcer healing. In surgical specimens of 27 gastric ulcer obtained from the surgical pathology archives, we examined immunohistochemically expressions of ERRP and EGFR, and cell proliferation by labeling proliferating cell nuclear antigen (PCNA-LI). In the neighboring gastric surface epithelium and pyloric gland mucosa of gastric ulcer tissue, ERRP immunoreactivity was expressed in cytoplasm as a perinuclear, dot-like pattern and staining was positive in over 70% of specimens. EGFR staining was positive in 40% of ulcer specimens. ERRP staining intensity was enhanced in proliferating foveolar epthelium of ulcer margin. The ERRP immunoreactivity in ulcer marginal cells revealed strong signal localized to the cytoplasm. Expression of ERRP was inversely correlated with PCNA-LI, while EGFR expression was positively correlated with PCNA-LI in gastric epithelial cells. However, there was no correlation between ERRP and EGFR expression in gastric epithelial cells. Our data indicate that expression of ERRP could play an important role in gastric ulcer healing. The inverse relationship between ERRP expression and PCNA-LI, suggests that ERRP may negatively regulate cell proliferation in gastric ulcer healing.
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