Liver-Intestine Cadherin in Intraepithelial Neoplasia of Intrahepatic Cholangiocarcinoma

Background/Aims: Liver-intestine cadherin (LI-cadherin) is a member of the cadherin superfamily and aberrant expression of LI-cadherin is associated with intestinal metaplasia. The aim of this study was to identify factors associated with LI-cadherin expression in biliary intraepithelial lesions of intrahepatic cholangiocarcinoma (ICC). Methodology: We evaluated the immunoreactivity of LI-cadherin, MUC2, CDX2, MUCSAC and HGM, according to the grade of biliary intraepithelial lesion in 16 resected specimens of ICC without hepatolithiasis. Results: A total of 168 biliary intraepithehal lesions were classified into four grades: reactive change (42 lesions), biliary intraepithelial neoplasia (BillN)-1 (10 lesions), BillN-2 (40 lesions) and BillN-3 (76 lesions). Biliary intraepithelial lesions were classified into three mucin phenotypes: null (46 lesions), gastric (97 lesions) and gastrointestinal phenotype (25 lesions). LI-cadherin expression was found in 45 (27%) of 168 biliary intraepithelial lesions. BilIN-2/3 (p<0.001), gastrointestinal phenotype (p=0.006) and CDX2 expression (p=0.002) were significantly associated with LI-cadherin expression. Logistic regression analysis revealed that BilIN-2/3 (p=0.002) was the only independently significant factor associated with LI-cadherin expression. Conclusions: The grade of BilIN in dependently correlates with LI-cadherin expression in biliary intraepithelial lesions of ICC without hepatoli thiasis, whereas the mucin phenotype or CDX2 expression does not.