Overexpression of Cyclooxygenase-2 Is Associated with a Favorable Prognostic Phenotype in Breast Carcinoma

Abstract

Objectives: Cyclooxygenase (COX) is the rate-limiting enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. The purpose of the present study was to investigate the involvement of COX-2 protein in breast cancer biological behavior through its correlation with the well-known clinicopathological parameters and the expression of p53, c-erbB-2, topoisomerase IIα (topoIIα) and peroxisome proliferator-activated receptor (PPARγ) proteins, as well as its effect on patients’ survival. Methods: We performed immunohistochemistry to detect COX-2, estrogen receptor (ER), progesterone receptor (PR), p53, c-erbB-2, topoIIα and PPARγ proteins in 175 cases of invasive breast carcinomas. The results were elaborated by statistic analysis. Results: Cytoplasmic expression of COX-2 was detected in 66.9% of breast carcinoma samples and was inversely correlated with both nuclear and histological grade (p < 0.0001 and p = 0.039, respectively), whereas its association with PR was found to be positive (p = 0.016). COX-2 expression was inversely correlated with topoIIα and p53 (p = 0.033 and p = 0.002, respectively), whereas its association with PPARγ was parallel (p < 0.0001). In addition, c-erbB-2 of tumor cells was inversely correlated with COX-2 in stromal cells of the tumor (p = 0.011). Neither univariate nor multivariate analysis demonstrated any association between COX-2 expression and patient overall or disease-free survival. Conclusions: The current data suggest that increased expression of COX-2 may be related to breast carcinomas with less aggressive phenotype. This suggestion is further supported by the positive correlation between COX-2 and PPARγ, since the latter is considered to be indicative of a less malignant phenotype of tumor cells.

Elevated Hu-Antigen Receptor (HuR) Expression is Associated with Tumor Aggressiveness and Poor Prognosis but not with COX-2 Expression in Invasive Breast Carcinoma Patients

“…High COX-2 expression was also associated with favorable patients' prognosis. These findings are in accordance with previous data [42]. Moreover, COX-2 expression was inversely associated with tumor size, disease stage and HER-2 expression and positively with ER expression, at a non-significant level though.…”

COX-2 and PPAR-γ Confer Cannabidiol-Induced Apoptosis of Human Lung Cancer Cells

“…In line with these data, overexpression of COX-2 decreased proliferation and increased apoptosis of osteosarcoma cells (43) and protected rather than sensitized animals to experimental skin tumor development (44). In addition, clinical data revealed a correlation between COX-2 expression and a less aggressive breast cancer phenotype (45). On the other hand, a rather protumorigenic function of COX-2 is supported by investigations that showed COX-2-derived PGs to decrease tumor cell apoptosis (46) and to increase tumor cell proliferation (47), invasion (47), and angiogenesis (30,31).…”

Cyclooxygenase-2 and the inflammogenesis of breast cancer

“…Molecular studies from multiple laboratories reveal that adenocarcinoma of the breast is characterized by aberrant over-expression of COX-2 by breast cancer epithelial cells [24,[33][34][35][36][37][38] . As shown by Karmali et al [116] Rose et al [117] , and others [33][34][35][36][37][38] , arachidonic acid production, COX-2 expression, and prostaglandin biosynthesis are increased in vivo by dietary n-6 polyunsaturated fatty acids (n-6-PUFAs) such as unconjugated linoleic acid, and decreased by n-3-PUFAs such as linolenic acid. High dietary intake of n-6-PUFAs may therefore be an important factor in the induction of constitutive COX-2 expression.…”

“…The study revealed the presence of COX-2 protein in 13 of 13 invasive human breast tumors, but not in samples of normal breast tissue. There was a statistically significant linear association between COX-2 and high (> 50%) tumor cell density (P < 0.01) with COX-2 protein localized to tumor cells.Subsequently, molecular biologists from multiple independent laboratories have consistently observed COX-2 over-expression in all stages of breast cancer [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] . Figure 1 shows the mean frequency of specimens over-expressing COX-2 in the progression of mammary carcinogenesis.…”