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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.

Claudins (CLDNs) are essential proteins of tight junctions. Changes in their expression pattern have been demonstrated in a number of tumors. CLDNs-3 and -4 are receptors of the Clostridium perfringens enterotoxin, cytolytic effects of the toxin are well known. The aim of our studies was to compare the different CLDN expression patterns in normal pancreas cells, pancreatic endocrine tumors, adenocarcinomas, mucinous cystic tumors and acinar cell carcinomas. Expressions of CLDN-1, -2, -3, -4 and -7 proteins were examined using immunohistochemical as well as RT-PCR techniques and the following observations were made: 1.) In addition to the well-known CLDN-1 and -4 expression CLDN-2, -3 and -7 proteins were demonstrated in ductal cells, while CLDN-3 and -7 proteins showed expression in acinar cells. Expression of CLDNs-3 and -7 was manifest in endocrine cells. 2.) CLDN-3 and -7 proteins showed high expression in endocrine tumors, CLDN-1, -2, and -4 proteins in exocrine tumors. This is the first description of CLDN protein expression in endocrine tumors. 3.) The level of CLDN-1, -4 and -7 protein expression in borderline cystic tumors is in between that of benign and malignant tumors. This supports the sequential development theory regarding mucinous cystic tumors. 4.) This is a first review on childhood acinar cell carcinoma causing Cushing syndrome. According to our results the following conclusions are made. 1.) The presence of CLDN-3 refers to endocrine differentiation. The adenocarcinomas and cystic mucinous tumors of exocrine origin denoted CLDN-1, -2, -4 and -7 positivity, whereas acinar cell carcinomas expressed only CLDN-1 and -2. Considering the CLDN expression observed in normal pancreas cells, it can be established that CLDN-1, -2 and -4 proteins are definitely markers of ductal differentiation, CLDN-1 protein of acinar and CLDN-3 of endocrine differentiation. 2). The increased CLDN-4 expression in adenocarcinomas and mucinous cystic tumors, as well as the high CLDN-3 expression in endocrine tumors may open up new prospects in the targeted therapy of these tumors. 3). The claudin expression pattern of pancreas tumors may be employed in the differential diagnosis of these tumors and may be of help in deciding dignity.