title: COX-2 expression in invasive breast cancer: correlation with prognostic parameters and outcome.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. anassar@emory.edu
authors.forename: Aziza
authors.initials: A
authors.lastname: Nassar
authors.forename: Anu
authors.initials: A
authors.lastname: Radhakrishnan
authors.forename: Isabel A
authors.initials: IA
authors.lastname: Cabrero
authors.forename: George
authors.initials: G
authors.lastname: Cotsonis
authors.forename: Cynthia
authors.initials: C
authors.lastname: Cohen
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology; D002277:Carcinoma / Q000175:diagnosis* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human