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Cyclo-oxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer
  1. C Costa1,
  2. R Soares2,
  3. J S Reis-Filho1,
  4. D Leitão1,
  5. I Amendoeira3,
  6. F C Schmitt4
  1. 1Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias S/N, 4200-Porto, Portugal
  2. 2Molecular Oncology Unit, Department of Pathology, Instituto Português de Oncologia do Porto, 4200-Porto, Portugal
  3. 3Department of Pathology, Hospital de São João, 4200-Porto, Portugal
  4. 4Medical Faculty, Porto University, Porto, Portugal
  1. Correspondence to:
 Dr F C Schmitt, Instituto de Patologia e Immunologia Molecular da Universidade do Porto, Rua Dr. Roberto Frias, s/n, 4200 Porto, Portugal;


Aims: Cyclo-oxygenases 1 and 2 (COX-1 and COX-2) are key enzymes in prostaglandin biosynthesis. COX-2 is induced by a wide variety of stimuli, and present during inflammation. COX-2 overexpression has been observed in colon, head and neck, lung, prostate, stomach, and breast cancer. In colon and gastric cancer, COX-2 expression was associated with angiogenesis. The aim of this study was to determine the relation between COX-2 expression and angiogenesis in breast cancer, and to correlate the expression of this enzyme with classic clinicopathological parameters.

Methods: COX-2 expression was investigated by immunohistochemistry and western blotting analysis. The expression of COX-2 was then related to age, histological grade, nodal status, oestrogen receptor status, p53 expression,c-erb-B2 overexpression, mitotic counts, MIB-1 labelling index, apoptotic index, sialyl-Tn expression, transforming growth factor α expression, microvessel density, and disease free survival in 46 patients with invasive ductal breast carcinoma.

Results: By means of immunohistochemistry, COX-2 expression was detected in eight of the 46 carcinomas studied. Western blotting showed COX-2 protein expression in the same breast tumours, but not in normal adjacent tissues. The density of microvessels immunostained with anti-F-VIII related antigen was significantly higher in patients with COX-2 expression than in those without expression (p = 0.03). In addition, COX-2 was significantly associated with the presence of sialyl-Tn expression (p = 0.02), lymph node metastasis (p = 0.03), a high apoptotic index (p = 0.03), and a short disease free survival (p = 0.03) in univariate analyses.

Conclusions: These data suggest that COX-2 expression is associated with angiogenesis, lymph node metastasis, and apoptosis in human breast cancer. Moreover, these results warrant further studies with larger series of patients to confirm the association with short disease free survival in patients with breast cancer.

  • cyclo-oxygenase 2
  • angiogenesis
  • breast cancer
  • COX, cyclo-oxygenase
  • ER, oestrogen receptor
  • F-VIII, factor VIII related antigen
  • HPF, high power field
  • STn, sialyl Tn
  • TGF-α, transforming growth factor α
  • VEGF, vascular endothelial growth factor
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