COX-2 expression is associated with an aggressive phenotype in ductal carcinoma in situ

Br J Cancer. 2004 Jan 26;90(2):423-9. doi: 10.1038/sj.bjc.6601534.


Cyclooxygenase type-2 (COX-2) is overexpressed in malignant tumours including breast cancers, though the mechanism of upregulation is unclear. This study aimed to determine COX-2 expression in ductal carcinoma in situ (DCIS) in comparison to invasive breast cancer (IBC) and normal breast, and also to investigate the relationship of COX-2 expression with HER-2 expression, oestrogen receptor (ER), tumour grade and cellular proliferation (Ki67) in DCIS. Cyclooxygenase type-2, HER-2, ER and Ki67 expression were determined by immunohistochemistry on paraffin tissue sections of DCIS (n=187), IBC (n=65) and normal breast reduction tissue (n=60). Cyclooxygenase type-2 expression in DCIS (67%, P<0.001) and IBC (63%, P<0.001) was significantly greater than in normal breast (23%). There was no difference in COX-2 expression level between DCIS and IBC (P=0.87) or between normal breast from reduction mammoplasty tissue and normal breast ducts around DCIS (22%, P=0.29). In DCIS, COX-2 expression was associated with higher cellular proliferation rates (P<0.0001), nuclear grade (P=0.003), with ER negativity (P=0.003) and with HER-2 positivity (P<0.0001). Cyclooxygenase type-2 expression is upregulated in in situ breast cancer and is associated with surrogate markers of an aggressive DCIS phenotype including nonoestrogen-regulated signalling pathways. Cyclooxygenase type-2 inhibition may potentially prevent the development of ER-positive and ER-negative breast cancers.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Carcinoma, Intraductal, Noninfiltrating / enzymology
  • Carcinoma, Intraductal, Noninfiltrating / genetics*
  • Carcinoma, Intraductal, Noninfiltrating / pathology*
  • Cell Division
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / therapeutic use
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Isoenzymes / biosynthesis*
  • Isoenzymes / pharmacology
  • Membrane Proteins
  • Middle Aged
  • Neoplasm Invasiveness
  • Phenotype
  • Prognosis
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Prostaglandin-Endoperoxide Synthases / pharmacology
  • Receptors, Estrogen / analysis
  • Retrospective Studies
  • Signal Transduction
  • Up-Regulation


  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Receptors, Estrogen
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases