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

J Clin Pathol. 2006 Jul;59(7):685-91. doi: 10.1136/jcp.2005.030650. Epub 2006 Feb 23.

Abstract

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.

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cyclooxygenase 2 / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • In Situ Hybridization, Fluorescence
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptor, ErbB-2 / metabolism
  • Signal Transduction
  • Survival Analysis
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Cyclooxygenase 2
  • Receptor, ErbB-2
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases