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Decrease of Deleted in Malignant Brain Tumour‐1 (DMBT‐1) expression is a crucial late event in intrahepatic cholangiocarcinoma
Author(s) -
Sasaki M,
Huang SF,
Chen MF,
Jan YY,
Yeh TS,
Ishikawa A,
Mollenhauer J,
Poustka A,
Tsuneyama K,
Nimura Y,
Oda K,
Nakanuma Y
Publication year - 2003
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1046/j.1365-2559.2003.01719.x
Subject(s) - hepatolithiasis , intrahepatic cholangiocarcinoma , medicine , immunohistochemistry , pathology , cancer research , hepatectomy , surgery , resection
Aims: To investigate the participation of DMBT‐1, a candidate tumour suppressor gene, in the development of intrahepatic cholangiocarcinoma via intraductal papillary neoplasm of the liver (IPN‐L) arising in hepatolithiasis. DMBT‐1 plays a role in mucosal immune defence. Methods and results: The expression of DMBT‐1 was examined immunohistochemically in biliary epithelial cells in hepatolithiasis ( n = 25), invasive and non‐invasive cholangiocarcinoma associated with hepatolithiasis ( n = 52), IPN‐L with hepatolithiasis ( n = 49), cholangiocarcinoma without hepatolithiasis ( n = 32), and 10 normal control livers. DMBT‐1 was expressed more frequently in the biliary epithelia of hepatolithiasis when compared with normal livers ( P < 0.05). DMBT‐1 expression was also frequent in IPN‐L (57%) and non‐invasive cholangiocarcinoma (79%). By contrast, DMBT‐1 was decreased in invasive cholangiocarcinoma with and without hepatolithiasis (50% and 30%, respectively) ( P < 0.05). The homozygous deletion of the DMBT‐1 gene was recognized in four (20%) of 20 cholangiocarcinoma tissues and two (50%) of four cholangiocarcinoma cell lines, corresponding to the reduction of DMBT‐1 expression. No deletion was detected in hepatolithiasis tissues. Conclusion: DMBT‐1 expression is increased in IPN‐L and non‐invasive cholangiocarcinoma as well as in biliary epithelia in hepatolithiasis. Decreased expression of DMBT‐1 and homozygous deletion of the DMBT‐1 gene in invasive cholangiocarcinoma suggest that they occur in the late stage of cholangiocarcinogenesis.