Tumor Biology

, Volume 32, Issue 3, pp 461–468 | Cite as

Methylation status and overexpression of COX-2 in Tunisian patients with ductal invasive breast carcinoma

  • Sondes Karray-Chouayekh
  • Fatma Trifa
  • Abdelmajid Khabir
  • Noureddine Boujelbene
  • Tahia Sellami-Boudawara
  • Jamel Daoud
  • Mounir Frikha
  • Ali Gargouri
  • Raja Mokdad-Gargouri
Research Article


Inflammation and hormonal signalling induce the cyclooxygenase-2 (COX-2) expression in solid tumours including breast cancer, which in turn affects cell proliferation, apoptosis and metastasis. The aim of this study was to investigate the expression of COX-2 and its association with clinical parameters, patient’s survival, hormones receptors (oestrogen, progesterone), ERBB2 and TP53 expression in 83 cases of infiltrating ductal breast carcinomas. Moreover, the methylation status at the CpG islands of the COX-2 gene promoter was also explored in 70 specimens. We showed that tumours exhibiting moderate to intense COX-2 immunostaining were significantly more frequent in patients over 45 years old (p = 0.027). Moreover, a high level of COX-2 expression correlated with a shorter survival time (p log-rank = 0.04) and was an independent prognostic factor (p = 0.022; HR 6.4; 95% CI = 1.3–31.4). On the other hand, hypermethylation of the COX-2 gene promoter was observed in 27% of cases and strongly associated with smaller tumours (<5 cm, p = 0.011). Furthermore, patients with methylated COX-2 pattern have a better 4-year disease-free survival (p = 0.022) as well as a prolonged overall survival (p log-rank test = 0.034). In conclusion, we showed that high COX-2 expression was associated with reduced survival and was an independent prognostic factor. However, hypermethylation of the COX-2 promoter correlated with a better overall survival in Tunisian patients with breast carcinoma.


Breast carcinoma Cyclooxygenase 2 Immunohistochemistry Methylation Prognosis Patients’ survival 



This work was supported by a grant from the Tunisian Ministry of Higher Education and Scientific Research.

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2010

Authors and Affiliations

  • Sondes Karray-Chouayekh
    • 1
  • Fatma Trifa
    • 1
  • Abdelmajid Khabir
    • 3
  • Noureddine Boujelbene
    • 3
  • Tahia Sellami-Boudawara
    • 3
  • Jamel Daoud
    • 3
  • Mounir Frikha
    • 3
  • Ali Gargouri
    • 1
  • Raja Mokdad-Gargouri
    • 1
    • 2
  1. 1.Unité de Génétique du Cancer et production de protéines thérapeutiques, Centre de Biotechnologie de Sfax, route Sidi MansourSfaxTunisia
  2. 2.University of SfaxSfaxTunisia
  3. 3.Centre Hospitalo-Universitaire Habib BourguibaSfaxTunisia

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