Liver-intestine cadherin expression is associated with intestinal differentiation and carcinogenesis in intraductal papillary mucinous neoplasm

Objectives: 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.