Overexpression of topoisomerase II alpha protein is a factor for poor prognosis in patients with luminal B breast cancer

Abstract

Background: The prognostic value and the best method of testing of topoisomerase II alpha (TOP2A) status have not been established in modern tailored therapy based on breast cancer subtype. Results: The frequencies of TOP2A overexpression and TOP2A amplified were 55.8% and 9.5%, respectively. TOP2A overexpression correlated strongly with nonluminal A subtype (χ2-test, p < 0.001). TOP2A overexpression was significantly associated with relapse-free survival in luminal B breast cancer (n = 316; log rank test, p < 0.001) but not in other breast cancer subtypes. Cox regression analysis showed that TOP2A overexpression is a significant prognostic factor in luminal B breast cancer (hazard ratio (HR) 4.00, 95% confidence interval (CI) 1.65-9.54, p = 0.002). TOP2A amplified was recognized in HER2 positive breast cancer (p < 0.001). In HER2 positive breast cancer, TOP2A amplified (HR 0.30, 95% CI 0.085-1.07, p = 0.063) appeared to be a better prognostic factor. Conclusion: In modern tailored therapy, TOP2A overexpression can be a poor prognostic factor in luminal B breast cancer. In contrast, TOP2A amplified could be a better prognostic factor in HER2 positive breast cancer. Materials and methods: Between May 2005 and April 2015, a total of 643 consecutive non-metastatic invasive breast cancers were evaluated for TOP2A amplified using fluorescence in situ hybridization analysis (FISH) and for TOP2A overexpression using the immunohistochemistry assay. FISH ratios of 2 or higher were designated as TOP2A amplified, and TOP2A staining > 10% was defined as TOP2A overexpression. The prognostic values of TOP2A amplified and TOP2A overexpression were retrospectively evaluated.