Overexpression of Cyclooxygenase-2 (COX-2) Correlates with Grade, Stage and Lymph Node Status in Colorectal Adenocarcinoma (CRC)

2 12 2009

KA Robstad, JD Choate, JS Ross, CE Sheehan and DM Jones, Department of Pathology, Albany Medical College, Albany, NY

Background: COX-2 is an inducible enzyme involved in prostaglandins metabolism that has been associated with cellular resistance to apoptosis both in normal and malignant epithelial cells.  Over-expression of COX-2 has been identified in various epithelial malignancies including colorectal CRC, but large scale studies of its prognostic significance for the disease have not been previously performed.

Design: Formalin-fixed, paraffin-embedded sections from 155 CRC were immunostained by an automated method (Ventana Medical Systems; Tucson, AZ) using mouse monoclonal COX-2 (clone CX-294, DAKO, Carpinteria, CA).  Cytoplasmic immunoreactivity was semi quantitatively evaluated based on both intensity (weak, moderate and intense) and distribution (focal <10%, regional 10 to 50% and diffuse >50%) and results were correlated with histologic and prognostic variables.

Result: Intense diffuse over-expression of COX2 was observed in 71/155 (46%) of CRC and correlated with increasing tumor grade [16% of grade 1 vs 51% of grade 2 vs 48% of grade 3, p=0.018); advanced AJCC stage (38% of stage I/II vs 53% of stage III/IV; p=0.048); and lymph node status (35% node negative vs 53% node positive, p=0.024).  COX2 over-expression did not correlate with disease recurrence or overall survival. On multivariate analysis, pathologic stage at diagnosis independently predicted patient survival.

Conclusion: Over-expression of COX-2 is associated with high tumor grade, advanced pathologic stage and positive lymph node status in CRC. Further study of COX-2 expression in CRC, particularly with reference to its clinical prognostic implications, appears warranted.

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