Immunohistochemical analysis of candidate gene product expression in the duodenal epithelium of children with coeliac sprue

Background-Coeliac sprue is a chronic disease, in which there is a characte ristic mucosal lesion of the small intestine and impaired nutrient absorpti on, which improves upon the withdrawal of wheat gliadins and related grain proteins from the diet. Biopsy specimens demonstrate diffuse enteritis with pronounced atrophy or total loss of villi. There is also a long term risk of malignant disease. Aims-To compare the immunoexpression of DCC (deleted in colon cancer), p53, E-cadherin, and beta -catenin in the duodenal mucosa of children with coel iac disease with that seen in children with no evidence of small intestinal disease. Methods-To gain more insight into the genetic and immunohistochemical alter ations of the duodenal epithelium in coeliac disease, 21 endoscopic biopsie s from children with coeliac disease and 10 duodenal biopsies from children without coeliac disease were immunohistochemically evaluated for p53, DCC, E-cadherin, and beta -catenin. Results-DCC expression was not reduced in patients with coeliac disease com pared with those without coeliac disease. p53 positive nuclear immunostaini ng was seen in seven of the 21 patients with coeliac disease. Positive nucl ear staining was seen mainly in the deep and the lateral aspects of the cry pts. All patients in the control group were negative for p53. In nine and t hree of the 21 patients with coeliac disease, respectively, the immunohisto chemical expression of E-cadherin and beta -catenin was reduced. However, b oth E-cadherin and beta -catenin immunostaining in the control group was no t altered. Conclusions-E-cadherin and beta -catenin were reduced in the duodenal epith elium of children with coeliac disease when compared with normal mucosa. p5 3 was overexpressed in the duodenal mucosa of patients with coeliac disease . The reduced expression of E-cadherin and beta -catenin and p53 overexpres sion. may contribute to the morphological changes seen in the small intesti nal mucosa in coeliac disease.