Claudins are the structures and functional components of tight junctions and have crucial roles in the maintenance of cell polarity, cellular arrangement, adhesion and paracellular transport. Various claudins are expressed in different epithelial cells and most tissues express multiple claudin proteins. The altered expression of claudins has been reported in various human carcinomas, but their expression in rectal well-differentiated endocrine neoplasms (carcinoid tumors), the most common endocrine tumors in the gastrointestinal tract, has yet to be examined. The expression of claudins-2, -3 and -4 in 16 rectal well-differentiated endocrine neoplasms was studied by immunohistochemical methods, and compared with their expression patterns in endocrine tumors of the pancreas and lung. According to previous reports, pancreatic endocrine tumors were positive for claudin-3 and negative for claudins-2 and -4, and a majority of lung carcinoid tumors showed no immunoreactivity to claudins-2, -3 and -4. However, our immunohistochemical study revealed that the rectal well-differentiated endocrine neoplasms showed diffuse positive immunoreactivity to claudins-2, -3 and -4. These results indicate that claudin expression depends on the site of origin of endocrine tumors. In addition, claudin-3 and -4 expression in rectal well-differentiated endocrine neoplasms suggests the possibility of a new therapeutic strategy. Claudins-3 and -4 are receptors for the cytotoxic Clostridium perfringens enterotoxin. This enterotoxin rapidly and specifically lyses cells expressing claudins-3 and -4 and has a potential application in cancer therapeutics. Accordingly, this enterotoxin may be applicable for the treatment of rectal well-differentiated endocrine neoplasms in the future in order to prevent unexpected metastatic recurrences after tumor resections, because these neoplasms have a relatively high incidence of metastases despite their small size.

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