[Study of claudins and prognostic factors in some gastrointestinal diseases]

Gastrointestinal tumors are highly ranked regarding tumoral mortality worldwide. The development and progression of gastrointestinal (GI) diseases go hand in hand with the changes of tight junctions (TJ). Claudins (CLDN) are the main TJ proteins, showing different expression by the different tissues, with the expressed CLDN profile being representative. I. We explored the changes of CLDN expression in Barrett's esophagus and related adenocarcinoma. CLDN2 and -3 expression in Barrett's esophagus was higher than in normal foveolar epithelium. Adenocarcinoma showed higher CLDN2 and -3 expression compared with normal and Barrett's epithelia. The similar CLDN expression profile of Barrett's esophagus and adenocarcinoma supports their sequential development. II. Gastric intestinal metaplasia showed higher expression of CLDN2, -3 and -4 as compared with normal antral foveolar mucosa. Tumors of small and large bowels exhibited higher CLDN2 expression when compared with normal epithelia. Colorectal adenoma and adenocarcinoma could not be differentiated according to their CLDN profile. Intestinal metaplasias of Barrett's esophagus and stomach show similar CLDN profile to small bowel epithelium. III. Studies on duodenal mucosa in celiac disease in childhood demonstrated CLDN2 and -3 expression to be higher than in normal mucosa. The expression was significantly higher in the distal part of the duodenum samples. This and the serious histological findings suggest that the distal duodenum is more adequate for biopsy testing. IV. Beside the epithelial cells, mesenchymal tumors express intercellular junctional proteins. Expression of claudins in gastrointestinal stromal tumors (GIST) and other mesenchymal neoplasia was also studied. The CLDN profile was found to be representative to the individual tumor. GIST, angiosarcoma, hemangioma, leiomyosarcoma and leiomyoma showed expression of various CLDNs. CLDN2 was detected in all entities. CLDN1, however, was found positive in leiomyosarcoma only. Leiomyoma, on the other hand, expressed only CLDN2. GISTs and leiomyosarcomas showed CLDN2, -3, -4, -5 and -7-expression. The angiogenic tumors revealed CLDN2 and -5 expression. The similar CLDN profile observable in GIST and leiomyosarcoma is suggestive of a histogenetic relationship. Smooth muscle and vessel tumors of different dignity could also be separated from each other based on CLDN profile.