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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
  1. K J Schmitz1,
  2. R Callies2,
  3. J Wohlschlaeger1,
  4. R Kimmig2,
  5. F Otterbach1,
  6. J Bohr1,
  7. H-S Lee1,
  8. A Takeda3,
  9. K W Schmid1,
  10. H A Baba
  1. 1Institute of Pathology, University Hospital of Essen, Essen, Germany
  2. 2Department of Obstetrics and Gynaecology, University Hospital of Essen
  3. 3Department of Internal Medicine, Gumma Paz Gakuen College, Gumma, Japan
  1. Correspondence to:
 H A Baba
 Institute of Pathology, University Hospital of Essen, D-45147 Essen, Hufelandstr 55, Germany; hideo.baba{at}


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.

  • 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

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  • Published Online First 23 February 2006

  • Competing interests: RK, FO AND KWS are members of the West German Cancer Centre Essen (WTZE), Essen, Germany. KJS, RC, JW, RK, FO, KWS and HAB are members of the University Breast Cancer Centre Essen, Essen, Germany.