Expression Of Cyclooxygenase-2 And Vascular Endothelial Growth Factor In Bladder Carcinoma And Their Relationship

PrefaceBladder carcinoma is one of the most common cancer and rate ranks the first among all cancers in urology tumors . It is important to investigate the mechanism of carcinogenesis and the new strategy of prevention and therapy . The carcinogenesis and development of bladder carcinoma is multistage and associated with lesions of esophagus . Long - term lesions of esophageal mucosa result in dysplasia and carcinogenesis . Prostaglandin E₂ (PGE₂) increases during the repairing of these lesions and plays an important role in protection, repairing and cell renewing, however , it also contributes to carcinogenesis by affecting mitosis, suppressing apoptosis, degrading immunity and so on . Cyclooxygenase (COX) is the rate - limiting enzyme in the concersion of arachidonic acid to PGE2. Two isoform of COX have been identified : constitutive COX-1 and in-ducible COX-2. COX-2 is induced by inflammatory substance, growth factors and carcinogen. It contributes to the pathologic process of inflammation, cancer and others. COX-2 may exert benefical effects in tumor growth and invasion by suppressing cell apoptosis, facilitating cell proliferation, promoting angiogenesis in tumor, degrading extracellular matrix ( ECM). COX-2 make the new vessel growing mainly through up - regulation of vascular endothelial growth factor (VEGF). VEGF is the main factor in regulating angiogenesis and penetrating vessels, it can degrade basement membrane ( BM) , stimulate angiogensis and benefit tumor growth and invasion. Up to now, the study of COX-2 and VEGF expression in bladder carcinoma has not been reported.ObjectivesTo evaluate the role of COX-2 and VEGF in carcinogenesis, development, metastasis of bladder carcinoma as well as the relationship to angiogenesis and the clinicopathology of tumor, and to provide theoretical foundation for bladder carcinoma prevention and new clinical theropy using selective COX-2 inhibitor acting as a chemopreventive strategy and anti - angiogesis in tumor.Materials and methods50 cases of surgically resected bladder transitional cell carcinoma sample, 15 cases of normal bladder tissue were collected. Expressions of COX-2 and VEGF were observed by immunothistochemical staining ( SABC) method. Sati-stical analysis: The SPSS 10.0 statistical package program was used for all analysis. X² - test, Fisher' s exact probability test were used to analyze the data. P <0.05 were deemed significant.ResultsThe positive staining of COX-2 is mainly located in cytoplasm, minority located nucleus membrance. COX-2 protein was undetectable in normal bladder tissue. In bladder transitional cell carcinoma, the positive rate of COX-2 was 80% (30/50). There was significant differences (P < 0.05) when bladder carcinoma group compared with normal group. In the grade I , II t IH, the positive rates of COX-2 were 43% (6/14) ,54% (13/24) ,91.7% (11/12) respectively, There were no significant differences (P >0. 05) when the expression of COX-2 was compared with grade I and grade II . There were significant differences (P <0.05) between grade I and grade III, and, also significant differences( P < 0.05) between grade II and grade III. In the tumor stage, the expression was higer( P < 0. 05 ) in invasive tumor ( T₂ T₄ ) than in superficial tumor ( T_a ^T₁).The positive staining of VEGF is mainly located in cytoplasm, minority located nucleus membrance. COX-2 protein was undetectable in normal bladder tissue. In bladder transitional cell carcinoma, the positive rate of VEGF was 82% (32/50). There was significant differences (P < 0.05) when bladder carcinoma group compared with normal group. In the grade I , II , HI i the positive rates of VEGF were 50% (7/14) ,58% (14/24) ,91. 7% (11/12) respectively, There were no significant differences( P >0. 05) when the expression of VEGF was compared with grade I and grade II . There were significant differences (P <0.05) between grade I and grade III , and, also significant differences! P < 0.05) between grade II and grade III. In the tumor stage, the expression was higer( P < 0. 05 ) in invasion tumor ( T2 T4 ) than in superficial tumor ( Ta ^T1) Of 50 cases bladder carcinoma, 24 case were positive expression of both COX-2 and VEGF, while 12 cases were negative expression of both COX-2 and VEGF. There was close correlation between COX-2 and VEGF expression (P < 0.05).ConclusionThe expression of COX-2 increases in high - grade bladder transitional cell carcinoma, the over - expression of COX-2 is correlate with the stage of invasive tumor. It provides referencing index for research of not only the early phase of carcinogenesis but also the development and invasion of bladder carcinoma.The expression of VEGF increases in high - grade and high - stage bladder transitional cell carcinoma, the over - expression of VEGF is correlate with the stage of invasive tumor. It provides theoretical foundation for VEGF may have relationship with the carcinogenesis, development and invasion of bladder carcinoma.The expression of COX-2 is related to the expression of VEGF. It is indicated that there is a certain regulation between COX-2 and VEGF. They contribute to the angiogenesis and metastasis of bladder carcinoma in coordination.COX-2 and VEGF are correlated with the development and metastasis of...