Karray-Chouayekh Sondes, Trifa Fatma, Khabir Abdelmajid, Boujelbene Noureddine, Sellami-Boudawara Tahia, Daoud Jamel, Frikha Mounir, Gargouri Ali, Mokdad-Gargouri Raja
Unité de Génétique du Cancer et production de protéines thérapeutiques, Centre de Biotechnologie de Sfax, route Sidi Mansour, BP K 1177, Sfax 3018, Tunisia.
Tumour Biol. 2011 Jun;32(3):461-8. doi: 10.1007/s13277-010-0139-0. Epub 2010 Dec 10.
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.
炎症和激素信号传导可诱导包括乳腺癌在内的实体瘤中环氧合酶-2（COX-2）的表达，这反过来又会影响细胞增殖、凋亡和转移。本研究的目的是调查83例浸润性导管乳腺癌中COX-2的表达及其与临床参数、患者生存率、激素受体（雌激素、孕激素）、ERBB2和TP53表达的关联。此外，还对70份标本中COX-2基因启动子的CpG岛甲基化状态进行了探索。我们发现，45岁以上患者中COX-2免疫染色呈中度至强阳性的肿瘤明显更常见（p = 0.027）。此外，COX-2高表达与较短的生存时间相关（p对数秩检验 = 0.04），并且是一个独立的预后因素（p = 0.022；风险比6.4；95%置信区间 = 1.3 - 31.4）。另一方面，27%的病例中观察到COX-2基因启动子的高甲基化，且与较小的肿瘤（<5 cm，p = 0.011）密切相关。此外，COX-2甲基化模式的患者有更好的4年无病生存率（p = 0.022）以及更长的总生存期（p对数秩检验 = 0.034）。总之，我们表明COX-2高表达与生存率降低相关，并且是一个独立的预后因素。然而，在突尼斯乳腺癌患者中，COX-2启动子的高甲基化与更好的总生存期相关。
