Clinicopathological correlates of aspartyl (asparaginyl) beta-hydroxylase over-expression in cholangiocarcinoma.
Aspartyl (asparaginyl) beta-hydroxylase (AAH) expression in surgically resected intrahepatic cholangiocarcinoma significantly correlated with tumor size, growth type, differentiation, vascular invasion, and prognosis after surgery. AAH may have a role in regulating invasive or metastatic tumor cell growth of human intrahepatic cholangiocarcinoma.


BACKGROUND
Recent studies demonstrated increased expression of the AAH gene in the majority of cholangiocarcinomas. The present study was undertaken to determine the relationship between high or low levels of AAH expression and the clinical course of intrahepatic cholangiocarcinoma (ICC).


METHODS
AAH expression was examined in 50 surgically resected primary ICCs, 12 samples of normal liver, and 12 cases of primary sclerosing cholangitis (PSC). The sections were evaluated by immunohistochemical staining with the FB-50 monoclonal antibody to human AAH protein. The sections were examined under code and graded for relative levels of AAH immunoreactivity. The results were analyzed with respect to multiple clinical and histopathological variables to determine correlates of AAH expression in ICCs.


RESULTS
Forty-six of the 50 (92%) ICCs had AAH immunoreactivity, whereas the 12 normal liver and 12 PSC specimens were AAH negative. In the ICC specimens, the highest levels of AAH immunoreactivity were detected at the infiltrating margins that interfaced with uninvolved liver tissue, and the lowest levels occurred in the central portions of the tumors. Multivariate analysis demonstrated that high levels of AAH expression were correlated with tumor size (P < 0.05), infiltrative growth pattern (P < 0.01), aggressive histological grade (P < 0.01), vascular invasion (P < 0.05), and poor prognosis (P < 0.05).


CONCLUSIONS
These findings suggest that AAH has an important role in regulating invasive or metastatic tumor cell growth of human ICC, and that high levels of AAH expression correlate with poor prognosis.
Maeda
Takashi
T
Liver Research Center, Department of Medicine and Pathology, Rhode Island Hospital, Brown Medical School, 55 Claverick Street, 4th Floor Providence, RI 02903, USA.
Taguchi
Ken-ichi
K
Aishima
Shin-ichi
S
Shimada
Mitsuo
M
Hintz
Deborah
D
Larusso
Nicholas
N
Gores
Gregory
G
Tsuneyoshi
Masazumi
M
Sugimachi
Keizo
K
Wands
Jack R
JR
de la Monte
Suzanne M
SM
D000368:Aged; D001650:Bile Duct Neoplasms / Q000201:enzymology / Q000473:pathology* / Q000601:surgery; D001653:Bile Ducts, Intrahepatic / Q000201:enzymology / Q000473:pathology*; D018281:Cholangiocarcinoma / Q000201:enzymology / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000032:analysis*; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis
D006899:Mixed Function Oxygenases; C058291:aspartic acid 2-oxoglutarate-dependent dioxygenase