title: Methylation status and overexpression of COX-2 in Tunisian patients with ductal invasive breast carcinoma.
abstract: 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.
authors.affiliation: Unité de Génétique du Cancer et production de protéines thérapeutiques, Centre de Biotechnologie de Sfax, route Sidi Mansour, BP K 1177, Sfax 3018, Tunisia.
authors.forename: Sondes
authors.initials: S
authors.lastname: Karray-Chouayekh
authors.forename: Fatma
authors.initials: F
authors.lastname: Trifa
authors.forename: Abdelmajid
authors.initials: A
authors.lastname: Khabir
authors.forename: Noureddine
authors.initials: N
authors.lastname: Boujelbene
authors.forename: Tahia
authors.initials: T
authors.lastname: Sellami-Boudawara
authors.forename: Jamel
authors.initials: J
authors.lastname: Daoud
authors.forename: Mounir
authors.initials: M
authors.lastname: Frikha
authors.forename: Ali
authors.initials: A
authors.lastname: Gargouri
authors.forename: Raja
authors.initials: R
authors.lastname: Mokdad-Gargouri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D014416:Tunisia
chemical_list: D051546:Cyclooxygenase 2; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C496540:PTGS2 protein, human; C508053:ERBB2 protein, human