Analysis of cyclooxygenase-2 expression in human breast cancer: high throughput tissue microarray analysis

J Cancer Res Clin Oncol. 2003 Jul;129(7):375-82. doi: 10.1007/s00432-003-0459-1. Epub 2003 Jul 15.


Purpose: The objective of this study was to evaluate breast carcinomas for the expression of cyclooxygenase-2 (Cox-2) using a tissue microarray (TMA) and to determine its clinical and prognostic relevance.

Methods: We analyzed Cox-2 expression in 600 samples from 200 breast carcinomas immunohistochemically performing TMA technology and semiquantitative analysis. Results were correlated with various clinicopathological variables and follow-up data. Expression of estrogen receptor, progesterone receptor, Ki-67, and Her-2/neu-oncogene was analyzed and correlated with Cox-2 status.

Results: We observed a moderate or strong cytoplasmic staining for Cox-2 in 78 (40.6%) of breast carcinomas. Increased Cox-2 expression corresponded to higher pT stage ( P=0.038), amplification of Her-2/neu ( P=0.032), lymphovascular invasion ( P=0.006), a high MIB-1 labeling index (LI) ( P<0.001), and histological grading ( P=0.013). We also observed an inverse relationship between strong Cox-2 expression and estrogen and progesterone receptor content of tumors ( P=0.037 and P=0.010). However, we could not demonstrate a significant association between Cox-2 staining and overall survival or disease free survival time.

Conclusions: These results suggest that Cox-2 expression is significantly associated with less differentiated and more aggressive breast carcinomas and might therefore be a useful prognostic indicator as well as a target for therapy.

MeSH terms

  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cyclooxygenase 2
  • Disease-Free Survival
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Isoenzymes / metabolism*
  • Membrane Proteins
  • Prognosis
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Receptor, ErbB-4
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Survival Analysis


  • Isoenzymes
  • Membrane Proteins
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • ERBB4 protein, human
  • ErbB Receptors
  • Receptor, ErbB-4