Prognostic value of eicosanoid pathways in extrahepatic cholangiocarcinoma
Christian Möbius1, Gabi Aust, Marcus Wiedmann
1Department of Surgery II, University of Leipzig, Leipzig, Germany. Christian.Moebius@medizin.uni-leipzig.de
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.
Materials And 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).
Conclusion:
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.