Wild Peter J, Kunz-Schughart Leoni A, Stoehr Robert, Burger Maximilian, Blaszyk Hagen, Simon Ronald, Gasser Thomas, Mihatsch Michael, Sauter Guido, Hartmann Arndt
Institute of Pathology, University of Regensburg, Regensburg D-93053, Germany.
Int J Oncol. 2005 Aug;27(2):385-91.
To investigate whether protein expression of cyclooxygenase 2 (COX2) is associated with tumor phenotype, immunohistochemical alterations, and clinical outcome in urinary bladder cancer (BC). Tissue microarrays (n = 776) were used to analyze COX2, P53 and the Ki-67 labeling index immunohistochemically. A monoclonal mouse antibody was used after heat-induced antigen retrieval. COX2 expression was scored semiquantitatively (0-3+). COX2 expression was detected in 60% (368/617) of urothelial BC. Positive COX2 staining was seen in 77.8% (140/182) of muscle invasive urothelial BC, compared to 35% (7/20) of muscle invasive squamous cell carcinomas (p < 0.001). COX2 protein expression was associated with advanced tumor stage (p < 0.0001), high-grade histology (p < 0.0001), solid growth pattern in invasive BC (pT1-4, p = 0.02), high Ki-67 labeling index (p < 0.0001), and positive P53 IHC (p < 0.001). COX2 expression was not associated with survival, recurrence, and progression in clinically relevant subgroups (pTa, pT1, pT2-4). Expression of COX2 is common in advanced BC with poor prognostic characteristics, supporting efforts to initiate clinical trials on the efficacy of COX2 inhibitors in the adjuvant treatment of high-risk urinary BC.
为研究环氧化酶2(COX2)的蛋白表达是否与膀胱癌(BC)的肿瘤表型、免疫组化改变及临床结局相关。使用组织微阵列(n = 776)对COX2、P53和Ki-67标记指数进行免疫组化分析。热诱导抗原修复后使用单克隆小鼠抗体。COX2表达进行半定量评分(0 - 3+)。在60%(368/617)的尿路上皮性BC中检测到COX2表达。在77.8%(140/182)的肌层浸润性尿路上皮性BC中可见COX2阳性染色,相比之下,肌层浸润性鳞状细胞癌中为35%(7/20)(p < 0.001)。COX2蛋白表达与肿瘤晚期(p < 0.0001)、高级别组织学(p < 0.0001)、浸润性BC中的实体生长模式(pT1 - 4,p = 0.02)、高Ki-67标记指数(p < 0.0001)及P53免疫组化阳性(p < 0.001)相关。在临床相关亚组(pTa、pT1、pT2 - 4)中,COX2表达与生存、复发及进展无关。COX2表达在具有不良预后特征的晚期BC中常见,支持开展关于COX2抑制剂在高危尿路上皮性BC辅助治疗中疗效的临床试验。