Liver-intestine cadherin in intraepithelial neoplasia of intrahepatic cholangiocarcinoma.
OBJECTIVE
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).


METHODS
We evaluated the immunoreactivity of LI-cadherin, MUC2, CDX2, MUC5AC and HGM, according to the grade of biliary intraepithelial lesion in 16 resected specimens of ICC without hepatolithiasis.


RESULTS
A total of 168 biliary intraepithelial lesions were classified into four grades: reactive change (42 lesions), biliary intraepithelial neoplasia (BilIN)-1 (10 lesions), BilIN-2 (40 lesions) and BilIN-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 independently correlates with LI-cadherin expression in biliary intraepithelial lesions of ICC without hepatolithiasis, whereas the mucin phenotype or CDX2 expression does not.
Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Makoto
M
Inoue
Yoichi
Y
Ajioka
Toshifumi
T
Wakai
Masaaki
M
Takamura
Pavel
P
Korita
Yoshio
Y
Shirai
Katsuyoshi
K
Hatakeyama
D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic; D000071616:CDX2 Transcription Factor; D015820:Cadherins / Q000032:analysis / Q000502:physiology*; D018281:Cholangiocarcinoma / Q000145:classification / Q000473:pathology*; D005260:Female; D018398:Homeodomain Proteins / Q000032:analysis; D006801:Humans; D008113:Liver Neoplasms / Q000145:classification / Q000473:pathology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D055262:Mucin-2 / Q000032:analysis
C490584:CDH17 protein, human; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D015820:Cadherins; D018398:Homeodomain Proteins; C524625:MUC2 protein, human; D055262:Mucin-2