Loss expression of uroplakin III is associated with clinicopathologic features of aggressive bladder cancer.
OBJECTIVE
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.
Matsumoto
Kazumasa
K
Department of Urology, School of Medicine Kitasato University, Tokyo, Japan. kazumasa@cd5.so-net.ne.jp
Satoh
Takefumi
T
Irie
Akira
A
Ishii
Junichiro
J
Kuwao
Sadahito
S
Iwamura
Masatsugu
M
Baba
Shiro
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D018740:Genetic Heterogeneity; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology; D060171:Uroplakin III
D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; C554660:UPK3A protein, human; D060171:Uroplakin III