Abstract：
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.
journal_name
Urologyjournal_title
Urologyauthors
Matsumoto K,Satoh T,Irie A,Ishii J,Kuwao S,Iwamura M,Baba Sdoi
10.1016/j.urology.2007.11.128subject
Has Abstractpub_date
2008-08-01 00:00:00pages
444-9issue
2eissn
0090-4295issn
1527-9995pii
S0090-4295(07)02519-8journal_volume
72pub_type
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