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Distinct expression patterns of claudin‐1 and claudin‐4 in intraductal papillary–mucinous tumors of the pancreas

The expression of claudin‐4 was investigated in human pancreas, pancreatic ductal adenocarcinomas, and intraductal papillary–mucinous tumors of the pancreas (IPMT), and compared with that of claudin‐1. In human adult pancreatic specimens, both claudin‐1 and claudin‐4 were immunohistochemically found in main and branching pancreatic ducts, terminal ductules and acinic cells, with the exception of endocrine cells. Of 12 cases of pancreatic ductal adenocarcinoma, 11 (92%) had positive immunostaining for claudin‐4, and seven (58%) for claudin‐1. In 44 lesions of 22 cases of IPMT, including six hyperplastic foci distant from the main lesions, clauidin‐1 was positive in three out of six (50%) hyperplastic foci, 14 out of 17 (82%) adenomas, three out of 10 (30%) borderline tumors, two out of six (33%) non‐invasive carcinomas, and one out of five (20%) invasive carcinomas, producing a statistically negative correlation with histological tumor grades. In contrast, claudin‐4 was negative in the six hyperplastic foci, and positive in four out of the 17 (24%) adenomas, five out of the 10 (50%) borderline tumors, five out of the six (83%) non‐invasive carcinomas, and four out of the five (80%) invasive carcinomas, producing a statistically positive correlation with histological tumor grades. On study of IPMT subtypes, claudin‐1 was positive in nine out of 10 (90%) clear‐cell types, seven out of 20 (35%) dark‐cell types, and four out of eight (50%) compact‐cell types. In contrast, claudin‐4 was positive in two out of the 10 (20%) clear‐cell types, 13 out of the 20 (65%) dark‐cell types, and three out of the eight (38%) compact‐cell types. These distinct expression patterns of claudin‐1 and claudin‐4 suggest that both claudins serve as useful molecular markers for the tumor classification of IPMT.