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. 2007 Feb;450(2):135-41.
doi: 10.1007/s00428-006-0355-6.

Elevated expression of cyclooxygenase-2 is a negative prognostic factor for overall survival in intrahepatic cholangiocarcinoma

Klaus Jürgen Schmitz  1 , Hauke Lang, Jeremias Wohlschlaeger, Henning Reis, Georgios Charalambos Sotiropoulos, Kurt Werner Schmid, Hideo Andreas Baba
Affiliations

Elevated expression of cyclooxygenase-2 is a negative prognostic factor for overall survival in intrahepatic cholangiocarcinoma

Klaus Jürgen Schmitz et al. Virchows Arch. 2007 Feb.

Abstract

The production of prostaglandins is regulated by cyclooxygenases (COXs), which also have a role in tumour development and progression in various human malignancies, including cholangiocarcinoma. Limited information is available of the correlation of COX-2 protein expression and prognosis in intrahepatic cholangiocarcinoma (ICC). The aim of the present study was to determine the clinical significance of COX-2 expression in ICC. In addition the correlation of COX-2 expression and apoptosis/proliferation was analysed. COX-2 expression was determined immunohistochemically in 62 resected ICCs. Proliferation was assessed using Ki67-immunohistochemistry, and apoptosis was measured with the TdT-mediated dUTP nick-end-labelling technique. COX-2 was identified as an independent prognostic factor (P = 0.028) in resected ICC by survival analysis. High levels of COX-2 expression were found to be associated both with reduced apoptosis and increased proliferation of tumour cells. This study demonstrates the independent prognostic value of the COX-2 expression in resected ICC, thus, offering a potential additional adjuvant therapeutic approach with COX-2 inhibitors.

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Figures

Fig. 1
Fig. 1
Immunostaining for COX-2 in noncancerous intrahepatic bile duct epithelial cells. Whereas portal bile ducts distant from the ICC consistently lacked COX-2 immunostaining (asterisk, left side), bile duct epithelial cells (asterisk, right side) adjacent to ICC (arrow) exhibited cytoplasmic immunoreactivity of varying intensity. Notice the COX-2 protein expression in normal hepatocytes. Original magnification, ×400
Fig. 2
Fig. 2
Representative COX-2 immunostaining results in ICC. Missing COX-2 staining (left) in contrast to strong cytoplasmic COX-2 immunoreactivity in ICC tumour cells (right). Original magnification, 400×. Inset: positive control (colorectal carcinoma) with strong immunostaining
Fig. 3
Fig. 3
Kaplan–Meier survival curves in resected intrahepatic cholangiocarcinoma in relation to different COX-2 expression. Tumours with elevated COX-2 levels exhibit a significantly decreased overall survival (p = 0.036, Log Rank test)
See this image and copyright information in PMC

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