COX-2 in RP specimens strongly predicts cancer return

November 1, 2006

Miami-Expression of cyclooxygenase-2 (COX-2) in radical prostatectomy specimens is an independent predictor of prostate cancer recurrence, according to a study reported by researchers from the University of Miami's Miller School of Medicine.

In their study, investigators used immunohistochemical staining to characterize expression of COX-2 in archived prostate cancer specimens of 60 patients who had been operated on between 1992 and 1995. None of the patients had received neoadjuvant hormonal therapy prior to radical prostatectomy, and only two had had positive nodes. During follow-up ranging from 62 to 142 months, 23 men (38.3%) experienced biochemical recurrence and increased PSA.

Extent of staining was graded by three independent observers and was categorized as low or high. In univariate analysis, high COX-2 expression and Gleason score, preoperative PSA, extraprostatic extension, positive surgical margin, and seminal vesicle invasion were significant predictors of biochemical recurrence, although high COX-2 expression was associated with the greatest increased risk.

The results were published recently in the International Journal of Cancer (2006; 119:1082-7).

"Only preoperative PSA and Gleason sum have been shown to accurately predict prostate cancer recurrence," said co-author Bal L. Lokeshwar, PhD, associate professor of urology at the Leonard Miller School of Medicine. "However, the majority of men diagnosed with prostate cancer have a PSA in the range of 4.0 to 10.0 ng/mL and a biopsy Gleason score of 5 to 7, and so there is a need for additional prognostic variables that could help better identify men likely to have aggressive disease.

"Our findings suggest COX-2 expression may have such a role, but ours is a relatively small study that needs to be confirmed by other investigators. Replication of our findings would also underscore the importance of inflammatory factors in prostate cancer progression and support the concept that inflammatory pathways might be an important target for the treatment of men with this malignancy," he added.

Clues from previous research

In previous research, Dr. Lokeshwar and colleagues found that COX-2, the inducible form of COX, was highly expressed in an established, aggressive prostate cancer cell line and that pharmacologic suppression of COX-2 activity with celecoxib (Celebrex) reversed the cell line's metastatic potential and its resistance to chemotherapeutic drugs.