COX-2 (Cyclooxygenase-2) Expression Is Associated with Agressive Disease in Invasive Mammary Carcinoma
Konstantinos Linos, Christine Sheehan, Jeffrey Ross. Memorial Sloan-Kettering Cancer Center, New York, NY; Albany Medical College, Albany, NY
Background: COX-2 converts arachidonic acid to prostaglandin H2 and has been linked to aberrant cancer cell adhesion, proliferation, apoptosis, angiogenesis, and immune surveillance. COX-2 overexpression has been associated with adverse prognostic factors for breast cancer, but it has not been widely studied as a marker of clinical outcome for the disease.
Design: Formalin-fixed, paraffin-embedded tissue sections from 177 cases of invasive mammary carcinoma [127 ductal (IDC) and 50 lobular (ILC)] were immunostained by automated methods (Ventana Medical Systems Inc., Tucson, AZ) using mouse monoclonal COX-2 (clone CX-294, DAKO, Carpinteria, CA). Cytoplasmic immunoreactivity was semiquantitatively scored based on staining intensity and distribution and the results were correlated with morphologic and prognostic variables.
Results: COX-2 expression was variably identified in normal breast epithelium with accentuation of staining in micropapillary ductal epithelium. Cytoplasmic COX-2 overexpression was observed in 123/177 (70%) tumors; 89/127 (70%) IDC and 34/50 (68%) ILC. COX-2 overexpression correlated with tumor grade [83% grade 3 vs 67% grade 2 vs 56% grade 1, p=0.046], advanced stage [77% advanced stage vs 62% early stage, p=0.042], lymph node status [75% node positive vs 61% node negative, p=0.049], and disease-free survival [83% recurrent vs 65% non-recurrent, p=0.016]. Within the IDC subgroup COX-2 overexpression correlated with tumor grade [83% grade 3 vs 67% grade 2 vs 50% grade 1, p=0.032] and lymph node status [78% node positive vs 60% node negative, p=0.032]; while showing a trend for advanced stage [79% advanced stage vs 64% early stage, p=0.074]; while within the ILC subgroup, COX-2 overexpression correlated with disease-free survival [92% recurrent vs 59% non-recurrent, p=0.028] while showing a trend for association with ER negative tumors [91% ER negative vs 63% ER positive, p=0.077].Within the ER negative subgroup, a trend with disease-free survival [91% recurrent vs 70% non-recurrent, p=0.062] was noted. On multivariate analysis, advanced stage and ER negative status were independent predictors of disease-free survival; while advanced stage was an independent predictor of shortened overall survival.
Conclusions: COX-2 overexpression is associated with adverse prognostic factors in breast cancer including high tumor grade, advanced tumor stage and disease recurrence after primary therapy. Further study of COX-2 expression in mammary carcinoma appears warranted.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 36, Wednesday Morning