[Claudin expression in different pancreatic cancers and its significance in differential diagnostics]

Abstract

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.