Decreased expression of the epidermal growth factor receptor-family in ulcerative colitis

Ulcerative colitis is a severe inflammatory disease of the large bowel, which is histopathologically characterized by ulcerations, lymphocyte infiltrations in the mucosa and epithelial dysplasia. The etiology and the pathophysiological mechanisms which contribute to these changes are unknown. The epidermal growth factor receptor (EGFR), c-erbB-2 and c-erbB-3 are transmembrane growth factor receptors which regulate cell growth and differentiation. In the present study we analyzed the expression and localization of the EGFR, c-erbB2 and c-erbB3 in ulcerative colitis samples obtained from 11 patients (5 female, 6 male), using immunohistochemical and molecular techniques. For comparison normal colonic tissue samples were obtained from 8 previously healthy organ donors. Northern blot analysis demonstrated a 1.6-fold, 3.6-fold and 3.8-fold decrease (p < 0.05) of EGFR, c-erbB-2 and c-erbB-3 mRNA-levels, respectively in ulcerative colitis by comparison with normal colon tissue samples. In the normal colon, moderate to intense EGFR immunostaining was present in the epithelial layer of the tunica mucosa and in the lamina muscularis mucosae. c-erbB-2 immunostaining was weaker in the normal colon, but present in a similar distribution as the EGFR. c-erbB3 immunoreactivity was found in the epithelial layer and in the lamina muscularis in the normal colon samples. In ulcerative colitis the remaining epithelial structures and some vessels in the tela submucosa exhibited strong EGFR- and c-erbB-3- and weak c-erbB-2-immunoreactivity. Our findings indicate that the decrease in EGFR, c-erbB-2 and c-erbB-3 might play a role in the pathogenesis of ulcerative colitis. The reduced expression of this growth factor receptor familiy might contribute to the reduced regeneration of the mucosa in patients with ulcerative colitis.