Loss expression of uroplakin III is associated with clinicopathologic features of aggressive bladder cancer
Loss expression of uroplakin III is associated with clinicopathologic features of aggressive bladder cancer
复制标题
DOI：
10.1016/j.urology.2007.11.128
复制
发表时间：
2008-08-01
期刊：
影响因子：
2.1
通讯作者：
Baba, Shiro
中科院分区：
文献类型：
--
作者：
Matsumoto, Kazumasa;Satoh, Takefumi;Baba, Shiro
目的组织特异性表达在基因治疗中具有重要意义，可通过使用组织特异性启动子驱动治疗性基因表达来实现。尿路蛋白(UP)启动子是膀胱癌基因治疗的有力工具，但UP蛋白在膀胱中的作用尚不清楚。本研究旨在检测UP III在膀胱移行细胞癌组织中的表达，探讨UP III异质性在预测肿瘤复发和患者生存中的作用。方法采用免疫组织化学方法检测92例膀胱癌组织和38例正常膀胱组织中UP III的表达，并与病理特征和临床结果进行相关性分析。结果膀胱癌组织中UP III的表达明显低于正常对照组(P<；0.0001)。在25.3个月的中位随访期中，uP III表达缺失与高级别、肌肉浸润性癌、淋巴血管侵犯相关(P<；0.01)，并降低了癌症特异性生存期(P=0.04)。当调整标准病理特征的影响时，只有淋巴结转移与膀胱癌的进展(P=0.01)和死亡率(P=0.04)有关。结论UP III表达的缺失与膀胱癌侵袭淋巴管、病理分期和分级等已建立的生物学侵袭性标志物有关。UP III的表达对膀胱癌患者预后的预测价值有限，但由UP启动子驱动的基因治疗病毒载体可在高表达的TCC细胞中驱动治疗性基因的表达，而在侵袭性低表达的TCC细胞中则不能。
OBJECTIVES Tissue-specific expression is of key importance in gene therapy and can be achieved by using tissue-specific promoters to drive therapeutic gene expression. The uroplakin (UP) promoter is a powerful tool for bladder cancer gene therapy, but the role of UP protein in the bladder remains unknown. This study aimed to detect UP III expression in transitional cell carcinoma (TCC) of the bladder and to determine whether the role of UP III heterogeneity is associated with predicting disease recurrence and patient survival.METHODS Immunohistochemical staining for UP III was carried out in 92 archival radical cystectomy and 38 normal specimens and correlated with pathologic features and clinical outcomes.RESULTS UP III expression was significantly decreased in bladder cancer tissues compared with normal controls (P < 0.0001). Loss of UP III expression was associated with high-grade, muscle-invasive cancer, lymphovascular invasion (P < 0.01), and decreased cancer-specific survival at a median follow-up of 25.3 months (P = 0.04). When adjusted for the effects of standard pathologic features, only lymph node metastases were associated with bladder cancer progression (P = 0.01) and mortality (P = 0.04).CONCLUSIONS Loss of UP III expression is associated with established markers of biologically aggressive bladder cancer such as lymphovascular invasion, pathologic stage, and grade. UP III expression has limited prognostic value in patients with bladder TCC, but gene therapy viral vectors driven by the UP promoter would drive therapeutic gene expression in high-UP-expressing TCC cells, but not in aggressive low-UP-expressing TCC cells.