人膀胱癌组织中环氧化酶2的表达

Expression of Cyclooxygenase-2 in Human Transitional Cell Bladder Carcinomas

背景与目的:环氧化酶(cyclooxygenase,COX)是人体内合成前列腺素的限速酶。最近研究表明,环氧化酶2(COX-2)与肿瘤的生成有关。本研究通过检测COX-1和COX-2在人膀胱癌组织、正常膀胱粘膜以及膀胱炎症组织中的表达,探讨COX在膀胱癌发生发展中的作用。方法:应用逆转录聚合酶链反应(RT-PCR)和免疫组化法(Envision二步法),检测膀胱移行细胞癌和癌旁组织、正常膀胱粘膜以及膀胱炎症组织中COX-1和COX-2mRNA和蛋白的表达,并分析癌组织中COX的表达强度与肿瘤对应的各项病理参数之间的关系。结果:RT-PCR检测15例新鲜膀胱癌组织COX-2mRNA均阳性表达,5例肉眼所见的癌旁正常组织中仅1例阳性,两者差异有显著性;而COX-1mRNA在所有新鲜癌组织标本中均有结构性表达。免疫组织化学研究结果与RT-PCR结果相似,COX-2蛋白主要集中在肿瘤细胞胞浆内,阳性表达率为50%,正常膀胱粘膜(n=4)和膀胱慢性炎症组织(n=5)中没有表达;反之,COX-1蛋白主要表达在正常或炎症组织的平滑肌细胞上,肿瘤组织中为阴性表达。在40例膀胱移行细胞癌石蜡切片标本中,COX-2蛋白的表达强度与肿瘤的分级和分期有关,恶性度较高的Ⅲ级癌的表达水平高于Ⅰ级和Ⅱ级癌,浸润性癌(T2-4)也高于浅表性癌(Ta-1)。结论:COX-2mRNA和蛋白在人膀胱癌组织中表达增高,并与肿?

Background & Objectives: 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.