Overexpression of cyclooxygenase-2 is associated with a favorable prognostic phenotype in breast carcinoma

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 II alpha (topoII alpha) and peroxisome proliferator-activated receptor (PPAR gamma) 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, topoII alpha and PPAR gamma 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 expression was inversely correlated with topoII alpha and p53 (p = 0.033 and p = 0.002, respectively), whereas its association with PPAR gamma 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 PPAR gamma, since the latter is considered to be indicative of a less malignant phenotype of tumor cells. Copyright (C) 2005 S. Karger AG, Basel.