Korean J Gastroenterol.  2005 Jan;45(1):52-59.

Expression of Epidermal Growth Factor Receptor, ErbB2 and Matrix Metalloproteinase-9 in Hepatolithiasis and Cholangiocarcinoma

• Kim HJ
• Kim JS
• Kang CD
• Lee SJ
• Kim JY
• Yeon JE
• Park JJ
• Shim JJ
• Byun KS
• Bak YT
• Lee CH

Abstract

BACKGROUND/AIMS: Hepatolithiasis is a common disease in East Asia and presents as a histological feature of proliferative glands containing mucin. 5-10% of hepatolithiasis is known to be associated with cholangiocarcinoma. Recent studies reported that epidermal growth factor receptor (EGFR) could be activated through heparin binding- EGF cleavage by metalloproteinases. Matrix metalloproteinases (MMPs) which digest the extracellular matrix are required for cancer cell invasion and the expression of MMP-9 is known to be increased in cholangiocarcinoma. However, there has been few studies on the expressions and roles of EGFR and MMP in hepatolithiasis. This study was performed to clarify and compare the expressions of EGFR, erbB2 and MMP-9 in hepatolithiasis and cholangiocarcinoma. METHODS: Surgically resected liver tissues with hepatolithiasis (n=14), cholangiocarcinoma (n=20) and trauma (n=2 as controls) were included. The expressions of EGFR, erbB2 and MMP-9 in tissue samples were examined by immunohistochemistry using respective monoclonal antibodies. RESULTS: In traumatic livers, the expressions of EGFR, erbB2 and MMP-9 were all negative. The expression of EGFR was increased in hepatolithiasis group (79%, 11/14) compared with cholangiocarcinoma group (25%, 5/20) (p<0.05). The expression of erbB2 was detected only in cholangiocarcinoma (25%, 5/20). MMP-9 was increased in both hepatolithiasis (79%, 11/14) and cholangiocarcinoma (95%, 19/20) (p>0.05). CONCLUSIONS: EGFR expression appears to be the dominant component in periductular hyperplasia of hepatolithiasis and MMP-9 is upregulated not only in cholangiocarcinoma but also in hepatolithiasis. This study suggests that EGFR and MMP-9 are associated with cholangiocarcinoma and hepatolithiasis.

Keyword

Stone, Intrahepatic; Recepotor, Epidermal growth factor; Genes, erbB-2; Matrix metalloproteinases; Cholangiocarcinoma

MeSH Terms

Adult
Bile Duct Neoplasms/*metabolism
*Bile Ducts, Intrahepatic
Cholangiocarcinoma/*metabolism
English Abstract
Female
Gelatinase B/*analysis
Humans
Lithiasis/*metabolism
Liver Diseases/*metabolism
Male
Middle Aged
Receptor, Epidermal Growth Factor/*analysis
Receptor, erbB-2/analysis
Up-Regulation