Cytoplasmic induction and over‐expression of cyclooxygenase‐2 in human prostate cancer: implications for prevention and treatment

Abstract

Objective To assess the level and morphological distribution of cyclooxygenase (COX)-1 and -2 in human prostates and to determine any association with the Gleason grade of prostate cancer. Materials and methods The study comprised 30 samples from patients with benign prostatic hyperplasia (BPH) and 82 with prostate cancer. Immunohistochemistry was used to assess the expression of COX-1 and -2, and 13 samples were also assessed using immunoblotting (six BPH and seven cancers). Results For both BPH and prostate cancer, COX-1 expression was primarily in the ®bromuscular stroma, with variable weak cytoplasmic expression in glandular/neoplastic epithelial cells. In contrast, COX-2 expression differed markedly between BPH and cancer. In BPH there was membranous expression of COX-2 in luminal glandular cells and no stromal expression. In cancer the stromal expression of COX-2 was unaltered, but expression by tumour cells was signi®cantly greater (P=0.008), with a change in the staining pattern from membranous to cytoplasmic (P<0.001). COX-2 expression was signi®cantly higher in poorly differentiated than in well differentiated tumours (P<0.001). These results were supported by immunoblotting, which showed similar levels of COX-1 in both BPH and cancer, but four times greater expression of COX-2 in cancer than in BPH. Conclusion This is the ®rst study to assess the coexpression of COX-1 and COX-2 proteins in benign and malignant human prostates, and showed the induction and signi®cantly greater expression of COX-2 in cancer, which was also associated with tumour grade. The regular use of nonsteroidal anti-in¯am-matory drugs is associated with a reduced incidence of cancers. The present results provide the basis for a potential role for COX-2 inhibitors in the prevention and treatment of prostate cancer.

The Effect of Combined Therapy with Tamsulosin Hydrochloride and Meloxicam in Patients with Benign Prostatic Hyperplasia Symptoms and Impact on Nocturia and Sleep Quality

“…The regular use of nonsteroidal anti-inflammatory drugs is associated with a reduced incidence of cancers. The present results provide the basis for a potential role for COX-2 inhibitors in the prevention and treatment of prostate cancer (24). Despite such strong association between inflammation, COX-2, and BPH, clinical trials evaluating the effects of COX-2 inhibitors in LUTS and BPH are scarce (25).…”

Cyclooxygenase‐2 (cox‐2) expression is an independent predictor of prostate cancer recurrence

“…Several cytokines, chemokines and inflammatory enzymes are known to induce COX-2 expression. [53][54][55] The data analysis presented above for COX-2 staining intensity show for the first time that COX-2 expression can independently predict prostate cancer recurrence. The sensitivity, specificity and accuracy of COX-2 staining to predict biochemical recurrence Note that 62 months, 72 months and 100 months were used as a cut point for determining biochemical recurrence.…”

Cyclooxygenase-2 Expression Correlates with Local Chronic Inflammation and Tumor Neovascularization in Human Prostate Cancer

“…Our finding of an increased number of COX-2 positive cells in high-grade cancer is generally in line with previous observations (25 -27). These studies conclude that there is an up-regulation of COX-2 in prostate cancer and in some COX-2 staining is related to tumor differentiation (28,29). A more recent study, however, showed that COX-2 protein expression is not consistently elevated in prostate cancer and does not correlate with established clinical-pathologic risk factors such as Gleason score and pathologic stage (24).…”