Prognostic value of eicosanoid pathways in extrahepatic cholangiocarcinoma.
BACKGROUND
Chronic inflammation of the bile duct is linked to an increased risk for the development of cholangiocarcinoma. Arachidonic acid and linoleic acid oxidation through cyclooxygenase and lipoxygenase--two major pro-inflammatory pathways--have rarely been investigated in extrahepatic cholangiocarcinoma.


METHODS
Paraffin-embedded specimens from 51 resected adenocarcinomas of the extrahepatic bile duct were immunostained for cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) to evaluate their intracellular distribution and prognostic value.


RESULTS
Cholangiocarcinoma had significantly higher levels of 5-LOX and COX-2 expression compared with normal tissue (p = 0.015). High expression of nucleus-located 5-LOX was significantly associated with intensive staining for COX-2, (p = 0.023). Median disease-free survival (DFS) in patients with low expression of 5-LOX was significantly better than in patients with high expression of 5-LOX (log rank p = 0.046). DFS in patients with low COX-2 expression was also significantly better than DFS in patients with high COX-2 expression (log rank p = 0.0187).


CONCLUSIONS
The present study demonstrates that 5-LOX and COX-2 protein expression was increased in cholangiocarcinoma suggesting that these two enzymes might be of prognostic value and offer a potential additional adjuvant therapeutic approach to this disease.
Möbius
Christian
C
Department of Surgery II, University of Leipzig, Leipzig, Germany. Christian.Moebius@medizin.uni-leipzig.de
Aust
Gabi
G
Wiedmann
Marcus
M
Wittekind
Christian
C
Mössner
Joachim
J
Hauss
Johann
J
Witzigmann
Helmut
H
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000401:mortality; D017734:Bile Ducts, Extrahepatic; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000401:mortality; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D006801:Humans; D011379:Prognosis; D016019:Survival Analysis
D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2