Cyclooxygenase-2 expression in prostate cancer: An inconsistent therapeutic target

Objectives: To determine cyclooxygenase-2 (COX-2) expression patterns in primary prostate tissue of patients undergoing androgen deprivation therapy and in patients with early stage disease. Methods: Gene and protein expression analysis were performed in freshly resected prostate cancer tissue obtained from patients with advanced stage cancer who presented with bladder obstruction (n = 8). Local stage cancer specimens were collected from patients undergoing radical prostatectomy (RP) (n = 10). Expression studies in fresh specimens included quantitative real time polymerase chain reaction, western immunoblotting and immunohistochemistry (IHC). Mean COX-2 gene expressions were compared in both stages. In addition to evaluating protein expression by IHC in fresh specimens, an unrelated archival specimen set of 23 additional clinically matched, advanced and 20 local stage cancer specimens were also analyzed. The pooled (fresh and archival) specimen set (n = 30 each) was then used for evaluating protein expression by IHC. Thirty non-cancer archival specimens with benign prostate hyperplasia were similarly evaluated by IHC. Results: COX-2 m-RNA was detected in all specimens successfully processed for gene expression studies (15/18). No difference was observed in mean gene expression intensities of both stages. Positive expression by immunoblotting was detected in 2/6 advanced and 0/9 local stage specimens. Immunohistochemical analysis of the pooled specimen set detected 4/30 advanced and 0/30 local stage cancer specimen positivity. Positive staining was observed in 2/30 benign hyperplasia specimens as well. Conclusions: COX-2 is expressed inconsistently in prostate tissue of patients undergoing androgen deprivation and is absent in the early stage. Therapeutic targeting with specific inhibitors is therefore likely to benefit a subgroup of patients with advanced stage disease.