Cyclooxygenase-2 is frequently overexpressed in human breast cancers

Background: Cyclooxgenase (COX) enzymes convert arachidonic acid to prostaglandins. Overexpression of the inducible COX isoform, COX-2, has been shown to play an important role in eolorectal tumorigenesis, however, its role in human breast cancer remains unknown. Evidence suggests that the COX-2 and c-erbB-2 pathways may be inter-related. Methods: We analyzed COX-2 and c-erbB-2 expression in formalin-fixed, parafin-embedded primary breast carcinomas (n=58). adjacent ductal carcinoma in situ (DCIS, n=14) and two cases of DCIS without invasive cancer. Histology included ductal (n=44), lobular (n=2), and other (n=7). Clinical stage was as follows: I (n=15). HA,B (n=24). Ill (n= 12). IV (n=1). ER and PR negativity was found in 21% and 46% of cancers, respectively. COX-2 and c-erbB-2 expression were detected by immunohistochemistry using highly specific monoclonal antibodies. The intensity and percentage of COX-2-stained cells was determined and a weight score was calculated. Membranous c-erbB-2 staining intensity was graded (10-3-). C-erbB-2 gene amplification was analyzed by FISH (n=20). The relationship between COX-2 and eerB-2 and clinicopathological variables was sought. Results: Cytoplasmic. granular COX-2 expression was detected in epithelial cells in 32 of 44 (72%) invasive breast cancers and in 14 of 16 (87%) eases of adjacent DCIS. Normal breast epithelium adjacent to cancer frequently had local staining of similar or decreased intensity relative to adjacent neoplastic epithelia. Rare peritumoral stromal cell COX-2 staining was observed. In 27 of 44 (62%) invasive cancers, COX-2 staining was diffuse, found in at least 50% of tumor cells. c-erbB-2 membranous staining (2 or 3+) was detected in 17 of 57 (30%) invasive cancers all but two cases were amplified. No significant correlation was found between COX-2 and c-erbB2 or clinicopathological variables. Conclusion: Our results indicate that COX-2 is frequently overexpressed in invasive breast cancers and adjacent DCIS. COX-2 inhibitors may be useful in the chemoprevention and therapy of human breast cancer.