[Expression of cyclooxygenase-2 in human transitional cell bladder carcinomas].
OBJECTIVE
Cyclooxygenase(COX) is a rate-limiting enzyme in prostaglandin synthesis. Recent study suggested that COX-2 was associated with carcinogenesis. This study was designed to investigate the role of COX in the development and progression of bladder cancer through examining the expression of COX-1 and COX-2 in human bladder cancer tissue, normal bladder mucosa, and cystitis tissue.


METHODS
Reverse transcriptase-polymerase chain reaction(RT-PCR) and immunohistochemistry(Envision method) were applied to detect the mRNA and protein expression of COX-1 and COX-2 in bladder transitional cell carcinoma(BTCC), tissue adjacent to cancer, normal bladder mucosa, and chronic cystitis tissue. Furthermore, the relationship between COX expression level and cancer pathologic parameters was analyzed.


RESULTS
Using RT-PCR, all 15 frozen specimens from bladder cancer were shown to express COX-2 mRNA, while only 1 of 5 specimens from grossly normal mucosa adjacent to cancer expressed COX-2 mRNA, with significant difference. But COX-1 mRNA was expressed constitutionally in all of the fresh cancer tissue samples. The immunohistochemical result was analogous to RT-PCR result. COX-2 protein was mainly localized at cytoplasm of malignant cell (positive rate was 50%) but was not expressed in normal bladder mucosa (n = 4) and chronic cystitis tissues (n = 5). In contrast, COX-1 protein was mainly localized at smooth muscle cell of normal tissue and cystitis tissue(positive rate was 100%) but was not expressed in cancer tissue. In 40 paraffin embedded specimens of BTCC, the intensity of COX-2 expression was associated with tumor grade and stage. The level of COX-2 expression was higher in grade III tumor, than in grade I, II tumors, and was higher in invasive tumor (T2-T4) than in superficial tumor(Ta-T1).


CONCLUSIONS
The expression of COX-2 mRNA and protein was enhanced in human BTCC, and was associated with the malignant degree of the tumor, indicating that COX-2 may play a key role in the development and progression of BTCC.
Zhan
Jian
J
Department of Urology, First People's Hospital of Shanghai, Shanghai 200080, P. R. China.
Tang
Xiao-da
XD
D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000201:enzymology* / Q000473:pathology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D009367:Neoplasm Staging; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001743:Urinary Bladder / Q000201:enzymology*; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000473:pathology
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases