title: Liver-intestine cadherin expression is associated with intestinal differentiation and carcinogenesis in intraductal papillary mucinous neoplasm.
abstract: OBJECTIVE
  Intraductal papillary mucinous neoplasms (IPMN) are classified into four phenotypes according to the WHO classification. Recently, intestinal-type IPMN has been suggested to grow with a distinct carcinogenetic pathway. Like mucin 2, oligomeric mucus/gel forming (MUC2) and caudal-related homeobox 2 (CDX2), liver-intestine cadherin (LI cadherin) is an intestine-specific marker. We aimed to investigate the roles of LI cadherin expression in IPMN.
  
  
  METHODS
  We examined LI cadherin expression in 135 cases of IPMN by immunohistochemical staining and the quantitative real-time reverse-transcription polymerase chain reaction.
  
  
  RESULTS
  LI cadherin protein and mRNA levels were significantly higher in intestinal-type IPMN than in nonintestinal-type IPMN (protein level, p < 0.001; mRNA level, p = 0.0312). A positive correlation was found between protein and mRNA of LI cadherin (p = 0.0037). The positivity rates of LI cadherin expression were significantly higher in CDX2-positive cases than in CDX2-negative cases (p < 0.001). In 41 intestinal-type IPMNs, LI cadherin-positive rates tended to increase gradually, from IPMN with low-grade dysplasia (IPMN-L) to IPMN with an associated invasive carcinoma (IPMN-IC) [IPMN-L vs. IPMN with high-grade dysplasia (IPMN-H); p = 0.0357, IPMN-L vs. IPMN-IC; p = 0.0230] and positively correlated with the Ki-67 labeling index (p = 0.0408), whereas this tendency was not recognized in nonintestinal-type IPMNs.
  
  
  CONCLUSIONS
  LI cadherin is associated with an intestinal phenotype and an 'intestinal pathway' of carcinogenesis in IPMN.
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Morimatsu
authors.forename: Shinichi
authors.initials: S
authors.lastname: Aishima
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kayashima
authors.forename: Akifumi
authors.initials: A
authors.lastname: Hayashi
authors.forename: Kohei
authors.initials: K
authors.lastname: Nakata
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Oda
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Taguchi
authors.forename: Masazumi
authors.initials: M
authors.lastname: Tsuneyoshi
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis; D000071616:CDX2 Transcription Factor; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D055262:Mucin-2 / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C490584:CDH17 protein, human; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D015820:Cadherins; D018398:Homeodomain Proteins; C524625:MUC2 protein, human; D055262:Mucin-2