Lipoxygenases (LOX) and
cyclooxygenases (COX) are key mediators of
arachidonic acid metabolism. Recently, studies have reported that human
breast carcinomas aberrantly express LOX and
cyclooxygenase-2 (COX-2), and that decreased levels of
15-lipoxygenase (15-LOX) and raised levels of COX-2 and 12-LOX have prognostic value in patients with
breast cancer. 15-LOX was significantly reduced with increasing stage, and in patients who developed metastatic disease, local recurrence, and/or died. With high COX-2, patients developed local recurrence, died from
breast cancer and had reduced disease-free and disease-related overall survival in
estrogen receptor (ER)-negative but not ER-positive disease. COX-2 expression is also associated with increased angiogenesis,
lymph node metastasis, and Her2-neu overexpression. The purpose of this study is to evaluate COX-2 expression in
breast cancer and to determine its correlation with prognostic parameters and outcome. Five tissue microarrays were constructed from 43
breast carcinomas and 5 normal breast tissues, represented by 1 mm cores in triplicate from each of 3 foci. Tissue microarray cores were immunostained with monoclonal COX-2. Expression was assessed as intensity and scored as percentage of cells positive. Prognostic parameters and follow-up information were obtained from the hospital records of Mexican Oncology Hospital, Mexico, where the
carcinomas were diagnosed. Ninety-five percent (41/43) of the
breast carcinomas showed cytoplasmic COX-2 expression. COX-2 intensity and percentage of cells positive correlated significantly with size of
carcinoma (P=0.0271; P=0.0539, respectively). COX-2 intensity correlated significantly with histologic grade (P=0.0182). COX-2 did not correlate with outcome (disease-free and overall survival). There was no significant correlation between COX-2 and ER. In conclusion, COX-2 correlates with poor prognostic markers in
breast cancer (large
tumor size and high
tumor grade), but not with outcome. The therapeutic value of
COX-2 inhibitors in COX-2 positive
breast cancer patients requires further investigation.