title: Distinct expression patterns of claudin-1 and claudin-4 in intraductal papillary-mucinous tumors of the pancreas.
abstract: 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.
authors.affiliation: Department of Surgery, Jichi Medical School, 3311-1 Yakushiji, Miniamikawachi, Kawachi, Tochigi 329-0498, Japan.
authors.forename: Munetoshi
authors.initials: M
authors.lastname: Tsukahara
authors.forename: Hideo
authors.initials: H
authors.lastname: Nagai
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kamiakito
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Kawata
authors.forename: Norio
authors.initials: N
authors.lastname: Takayashiki
authors.forename: Ken
authors.initials: K
authors.lastname: Saito
authors.forename: Akira
authors.initials: A
authors.lastname: Tanaka
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000378:metabolism* / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D062445:Claudin-1; D062506:Claudin-4; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C568108:CLDN1 protein, human; C568157:CLDN4 protein, human; D062445:Claudin-1; D062506:Claudin-4; D008565:Membrane Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm