The Clinical Significance Of Expression Of Cyclooxygenase-2 And CPLA2 In Human Breast Cancer

Objective:Cyclooxygenase (COX) is a rate-limiting enzyme that converts arachidonic acid to prostaglandin, COX exists in two isoforms, COX-1 and COX-2. COX-1 is a constitutive enzyme that produces PGs for maintaining physiological functions, such as gastric cytoprotection, vascular homeostasis, and renal function. COX-2 is an inducible enzyme that produces PG involed inflammation and cell growth. Cox-2 is express in normal brain and kidney. COX-2 expression is stimulated by a number of inflammation, growth factors, oncogenes, lipopolysaccharides, and tumor promoters. Results of several studies using mose models of colon cancer and the results of clinical trails have shown COX-2 to be useful target for the prevent and treatment of cancer. Studies with several other epithelial cancers involving different organ site, e.g. breast prostate, bladder, lung, suggest that Cox-2 plays an important role in the pathogenesis of these cancers. Recent reports have demonstrated that the use of NSAIDs is associated with a reduction in human breast cancer risk and that breast cancer risk declines with increasing NSAID exposure. Studies from mouse of mammary tumorigenesis and from human breast cancer cell lines provide evidence that COX-2 overexpression plays an important role in the pathogenesis of malignant breast cancer in humans. This study was designed to investigate the role of COX-2 in the development and progression of breast cancer through examing the express of COX-2 and pathophysiological features in patients with breast cancer. Because of availability of effective and relatively safe COX-2 inhibitors, it should be soon possible to evaluate their effectiveness in the clinic for the prevention and treastment of breast cancer. It is likely the COX-2 inhibitors will be effective in the treastment regimens involving combination chemotherapies.Phospholipase 2(PLA 2) is another key enzyme in metabolism of arachidonic acid, and it participate in regulation of cell proliferation through catalysis the release of arachidonic acid and its metabolism product. It is reported that the activity and expression of cPLA2 are increased in human colon cancer, gastric carcinoma and hepatocellular carcinoma, which prompted cPLA₂ may play an important role in tumorigenesis. Methods:Expression of COX-2 protein was detected in 61 case if breast cancinoma tissues ang 15 case of adenosis of breast by immunohistochemistry method (Steptavidin-biotin immunoperoxidase method), the relationship between expression level of COX-2 and cPLA2 and cancer pathologic characteristic was analyzed.Immunohistochemistry method: Briefly, slides were deparaffinization, rehydrated, prolease K to repair the antigen. After washing the slides in PBS for 5 min, the slides were then in 3% H₂O₂ to quench endogenous peroxidase activity. After three washes in PBS, nonspecific bindings were blocked by treating slides with 10% goat serum. The slides were incubated overnight with antibody (dilution, 1:100) at 4℃. Next, after three washes in PBS, slides were incubated with goat biotinylated anti-rabbit immunoglobulin G for 15 min at 37°C, and then incubated with streptavidin-biotin complex peroxidase at room temperature for 30 min. The slides were stained with DAB and counterstained with hematoxylin after washing with PBS.Results:The expression of COX-2 is located in the intracytoplasm of epithelial cells. Positive expression of COX-2 was detected in 86.80% of the breast cancerous tissues and in only 20% of adenopathy tissues and there was significant diffrence in expression of COX-2 between cancer tissues and paracancerous tissues (P<0.05). The expression of COX-2 was positive correlated with the metastatic lymph nodes and clinical stage (P<0.05, P<0.01) but there was no correlation with age (P>0.05).The expression of cPLA2 is also located in the intracytoplasm of epithelial cells. Positive expression of cPLA2 was detected in 81.90% of the breast cancerous tissues and in only 13.3% of adenopathy tissues and there was significant diffrence in expression of cPLA2 between cancer tissues and paracancerous tissues (P<0.05). The expression of cPLA2 was positive correlated with the metastatic lymph nodes and clinical stage (P<0.05) but there was no correlation with age (P>0.05).Conclusion:COX-2 might play important role in the proliferation of breast cancer cells. The expression of COX-2 and cPLA2 are obviously up-regulated. The expression of COX-2 and cPLA2 are positive correlated with the metastatic lymph nodes and clinical stage (P<0.05) but there was no correlation with age. COX-2 might play important role in the proliferation of breast cancer cells.Presently studies show the selective COX-2 inhibitiors in various experimental cancer systems indicate that COX-2 is likely to be a useful target for prevention and treastment of many epithelial cancers including breast cancer. In the future, clinical trials are needed to determine whether combining COX-2 inhibitors with these drugs will improve their effectiveness and also help overcome the painful side effects associated with therapy-induced inflammation.