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.