Clinical significance of heme oxygenase-1 expression in non-muscle-invasive bladder cancer.
BACKGROUND
In several malignant diseases, elevated heme oxygenase-1 (HO-1) is associated with progression or resistance to chemotherapy. We evaluated the clinical significance of HO-1 expression in non-muscle-invasive bladder cancer.


METHODS
We examined 109 patients with non-muscle-invasive bladder cancer. The immunoexpression of HO-1, p53, and Ki-67 was analyzed using paraffin-embedded tissue from transurethral resection in comparison with the clinicopathological variables.


RESULTS
Positive expression of HO-1 was found in 66 of 109 tumors (61%), and the positivity of HO-1 correlated significantly with high tumor grade and the altered expression patterns of p53 and Ki-67. In our analysis of 16 cases treated by intravesical administration of anthracyclines, the positive expression of HO-1 correlated with poor disease-free survival (p = 0.015). In in vitro experiments using urothelial cancer cell lines, HO-1 upregulation was observed by exposure to doxorubicin. Moreover, siRNA-mediated suppression of HO-1 upregulation sensitized the urothelial cancer cells to doxorubicin.


CONCLUSIONS
Our findings suggested that resistance against anthracyclines correlated with HO-1 and expression analysis of HO-1 may be a useful predictive marker for intravesical administration of anthracyclines.
Miyake
Makito
M
Department of Urology, Nara Medical University, Nara, Japan. mm-ulo @ naramed-u.ac.jp
Fujimoto
Kiyohide
K
Anai
Satoshi
S
Ohnishi
Sayuri
S
Nakai
Yasushi
Y
Inoue
Takeshi
T
Matsumura
Yoshiaki
Y
Tomioka
Atsushi
A
Ikeda
Tomohiro
T
Tanaka
Nobumichi
N
Hirao
Yoshihiko
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000494:pharmacology; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000473:pathology; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000473:pathology
D018943:Anthracyclines; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D034741:RNA, Small Interfering; D004317:Doxorubicin; D051547:Heme Oxygenase-1