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.