[Expression of epidermal growth factor receptor, ErbB2 and matrix metalloproteinase-9 in hepatolithiasis and cholangiocarcinoma].
OBJECTIVE
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.
Kim
Hyo Jung
HJ
Department of Internal Medicine, Kangwon National University College of Medicine, Chuncheon, Korea.
Kim
Jae Seon
JS
Kang
Chang Don
CD
Lee
Sung Joon
SJ
Kim
Jin Yong
JY
Yeon
Jong Eun
JE
Park
Jong-Jae
JJ
Shim
Jae Jeong
JJ
Byun
Kwan Soo
KS
Bak
Young-Tae
YT
Lee
Chang Hong
CH
D000328:Adult; D001650:Bile Duct Neoplasms / Q000378:metabolism*; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000378:metabolism*; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D006801:Humans; D020347:Lithiasis / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D015854:Up-Regulation
D066246:ErbB Receptors; D020780:Matrix Metalloproteinase 9; D018719:Erb-b2 Receptor Tyrosine Kinases