title: Expression of claudin-4 (CLDN4) mRNA in intraductal papillary mucinous neoplasms of the pancreas.
abstract: Claudin-4, encoding a protein for tight junction formation and function, is highly overexpressed in pancreatic ductal adenocarcinoma and is also associated with invasive adenocarcinomas arising in intraductal papillary mucinous neoplasms of the pancreas. However, the expression pattern of claudin-4 during neoplastic progression of intraductal papillary mucinous neoplasms remains unknown. Using quantitative real-time reverse transcription-PCR, we analyzed claudin-4 mRNA in a panel of 14 pancreatic cancer cell lines and in formalin-fixed paraffin-embedded tissues from 80 patients with intraductal papillary mucinous neoplasms of different histological grades and papillary subtypes. Increased expression of claudin-4 was confirmed in all the pancreatic cancer cell lines tested as compared with normal ductal epithelial cells and fibroblast cultures. The claudin-4 expression was significantly higher in high-grade intraductal papillary mucinous neoplasms (borderline neoplasm and carcinoma) than in low-grade intraductal papillary mucinous neoplasms (adenoma) (P<0.0001). In addition, claudin-4 mRNA levels were significantly higher in intestinal-type intraductal papillary mucinous neoplasms than in non-intestinal-type intraductal papillary mucinous neoplasms based on papillary subclassification (P<0.0001). Our findings suggest that claudin-4 expression is associated with neoplastic progression of intraductal papillary mucinous neoplasms and, especially, with a distinct pathway to intestinal differentiation.
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tsutsumi
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sato
authors.forename: Lin
authors.initials: L
authors.lastname: Cui
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizumoto
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Sadakari
authors.forename: Hayato
authors.initials: H
authors.lastname: Fujita
authors.forename: Kenoki
authors.initials: K
authors.lastname: Ohuchida
authors.forename: Takao
authors.initials: T
authors.lastname: Ohtsuka
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takahata
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000145:classification / Q000235:genetics* / Q000473:pathology; D000236:Adenoma / Q000145:classification / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000145:classification / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D062506:Claudin-4; D005404:Fixatives; D005557:Formaldehyde; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007564:Japan; D008565:Membrane Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D010189:Pancreatic Juice / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D016612:Paraffin Embedding; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016707:Tissue Fixation / Q000379:methods; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C568157:CLDN4 protein, human; D062506:Claudin-4; D005404:Fixatives; D008565:Membrane Proteins; D012333:RNA, Messenger; D005557:Formaldehyde