Clinical implications and prognostic values of topoisomerase-II alpha expression in primary non-muscle-invasive bladder cancer.
OBJECTIVE
To investigate the association between expression levels of topoisomerase-II alpha (TOP-2alpha) and prognosis in primary non-muscle-invasive bladder cancer (NMIBC). TOP-2alpha, a marker of cell proliferation, has been assessed as a prognostic indicator in several types of cancer. However, currently available data on the role of TOP-2alpha in prognosis are inconsistent.


METHODS
Top-2alpha messenger ribonucleic acid (mRNA) levels were examined in 103 tumor specimens from patients with primary NMIBC by real-time polymerase chain reaction. Immunohistochemical staining was performed on 39 matched tumor samples. The median follow-up period for all patients was 51.8 months (range, 3.2-137).


RESULTS
The mRNA expression levels of TOP-2alpha were significantly elevated in subjects with high-grade (P<.001) and high-stage (P=.041) tumors as compared with subjects with low-grade and low-stage tumors. Kaplan-Meier estimates revealed significant variation in tumor recurrence and progression depending on the level of TOP-2alpha expression (log-rank test, P<.05). Multivariate Cox regression analysis revealed that the level of TOP-2alpha expression is a strong predictor of recurrence (hazard ratio, 2.507; 95% confidence interval, 1.228-5.116; P=.012) and progression (hazard ratio, 4.192; 95% confidence interval, 1.002-17.536; P=.049) for NMIBC. The results of immunohistochemical staining generally correlated with mRNA expression levels.


CONCLUSIONS
Enhanced expression of TOP-2alpha is positively associated with a high rate of recurrence and progression in NMIBC. Thus, TOP-2alpha represents a promising marker of prognosis for NMIBC.
Kim
Eun-Jung
EJ
Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk, South Korea.
Lee
Young-Suk
YS
Kim
Yong-June
YJ
Kim
Min-Ju
MJ
Ha
Yun-Sok
YS
Jeong
Pildu
P
Lee
Ok-Jun
OJ
Kim
Wun-Jae
WJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D015331:Cohort Studies; D016001:Confidence Intervals; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D055815:Young Adult
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D004250:DNA Topoisomerases, Type II