ORIGINAL ARTICLE

Overexpression of cyclo-oxygenase-2 is an independent predictor of unfavourable outcome in node-negative breast cancer, but is not associated with protein kinase B (Akt) and mitogen-activated protein kinase (ERK1/2, p38) activation or with Her-2/neu signalling pathways

K J Schmitz¹, R Callies², J Wohlschlaeger¹, R Kimmig², F Otterbach¹, J Bohr¹, H-S Lee¹, A Takeda³, K W Schmid¹ and H A Baba

¹ Institute of Pathology, University Hospital of Essen, Essen, Germany
² Department of Obstetrics and Gynaecology, University Hospital of Essen
³ Department of Internal Medicine, Gumma Paz Gakuen College, Gumma, Japan

Correspondence to:
Correspondence to:
H A Baba
Institute of Pathology, University Hospital of Essen, D-45147 Essen, Hufelandstr 55, Germany; hideo.baba{at}medizin.uni-essen.de

Background and aim: The production of prostaglandins is regulated by cyclo-oxygenases (COXs), which also have a role in tumour development and progression in various malignancies, including breast cancer. The mechanisms by which COX-2 contributes to unfavourable prognosis are still poorly understood. The association between expression of COX-2 and possible linked signalling pathways—namely, Akt, extracellular regulated kinases (ERK1/2), the stress-activated kinase p38 or Her-2/neu—is assessed in a series of 113 node-negative breast cancers.

Results: COX-2 was identified as an independent prognostic factor (p = 0.034) in node-negative breast cancer by survival analysis. The lack of a relationship between COX-2 expression and activated Akt, Erk1/2, p38 and Her-2/neu was indicated by statistical analysis.

Conclusions: The prognostic effect of COX-2 expression on lymph node-negative breast cancer is confirmed—COX-2 is probably not regulated by HER-2, Akt, Erk1/2 or p38. Further studies are necessary for the elucidation of the signalling pathways responsible for the modification of COX-2 expression and the increased aggressiveness of breast cancers overexpressing COX-2.

Abbreviations: COX, cyclo-oxygenase; ERK, extracellular regulated kinases; FAP, familial adenomatous polyposis; FISH, fluorescent in situ hybridisation; IHC, immunohistochemistry; MAPK, mitogen-activated protein kinase; NSAID, non-steroidal anti-inflammatory drug; pAkt, phospho-Akt; pERK, phospho-ERK; PGE₂, prostaglandin E₂; pp38, phospho-p38; SSC, sodium salt citrate

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Kuo, S.-H., Yeh, P.-Y., Chen, L.-T., Wu, M.-S., Lin, C.-W., Yeh, K.-H., Tzeng, Y.-S., Chen, J.-Y., Hsu, P.-N., Lin, J.-T., Cheng, A.-L. (2008). Overexpression of B cell-activating factor of TNF family (BAFF) is associated with Helicobacter pylori-independent growth of gastric diffuse large B-cell lymphoma with histologic evidence of MALT lymphoma. Blood 112: 2927-2934 [Abstract] [Full Text]  
• Dillon, M. F, Stafford, A. T, Kelly, G., Redmond, A. M, McIlroy, M., Crotty, T. B, McDermott, E, Hill, A. D, Young, L. S (2008). Cyclooxygenase-2 predicts adverse effects of tamoxifen: a possible mechanism of role for nuclear HER2 in breast cancer patients. Endocr Relat Cancer 15: 745-753 [Abstract] [Full Text]