Clinical Implications and Prognostic Values of Topoisomerase-II Alpha Expression in Primary Non-muscle-invasive Bladder Cancer

Objectives: 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.