Predictive value of topoisomerase II alpha protein for clinicopathological characteristics and prognosis in early breast cancer.

Abstract

PURPOSE:

Topoisomerase II alpha (TOP2A) has been identified as a proliferation marker, of which the most common method for detection is immunohistochemistry (IHC). However, the optimal cut-off of TOP2A expression regarding prognostic value remains controversial. This study was to identify the optimal cut-off value of TOP2A expression and its correlation with clinicopathological variables and prognosis in early stage breast cancer in China.

METHODS:

Between January 2013 and January 2015, a total of 1084 early breast cancer patients were enrolled. The optimal cut-off of TOP2A expression was assessed using the minimum P value approach. Correlations between TOP2A expression and clinicopathological characteristics were explored by the Spearman's correlation analysis, while the impact of TOP2A expression on disease-free survival (DFS) and overall survival (OS) was evaluated by the Kaplan-Meier methods. Univariate and multivariate Cox regression analyses were executed to identify statistically significant prognostic factors.

RESULTS:

The optimal cut-off value of TOP2A was recommended as 15%. Overall, 603 (55.6%) patients were TOP2A over-expression and 481 (44.4%) patients were TOP2A low expression. TOP2A over-expression was in positive associations with a higher Ki67 index (r = 0.83, P < 0.001), HER2 positive (r = 0.26, P < 0.001), a larger tumor size (r = 0.14, P < 0.001), and a higher histologic grade (r = 0.59, P < 0.001), and in a significantly negative correlation with hormone receptor (HR) positive expression (r =  - 0.40, P < 0.001) in early breast cancer. TOP2A over-expression significantly associated with worse DFS (P = 0.001) and OS (P < 0.001) and was an independent prognostic factor for both DFS (hazard ratio [HR] = 2.04; 95% confidence interval [95% CI] 1.30-3.18, P = 0.0018) and OS (HR = 3.54; 95%CI 1.53-8.23, P = 0.003) in stage I-II breast cancer patients.

CONCLUSION:

To our knowledge, this is the first study to recommend the optimal cut-off value of TOP2A expression in breast cancer. The TOP2A expression is significantly correlated with HER2 status, Ki67 index, tumor size, histologic grade and HR status, and could be a surrogate indicator for poor prognosis of early breast cancer.

• Authors: Yun Wu, Yiqun Han, Qing Li, Pin Zhang, Peng Yuan, Yang Luo, Ying Fan, Shanshan Chen, Ruigang Cai, Qiao Li, Hangcheng Xu, Yan Wang, Fei Ma, Jiayu Wang, Binghe Xu
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 193 Issue 2 Pg. 381-392 (Jun 2022) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 35297009 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Antigens, Neoplasm
• DNA-Binding Proteins
• Ki-67 Antigen
• Poly-ADP-Ribose Binding Proteins
• Receptor, ErbB-2
• DNA Topoisomerases, Type II
• TOP2A protein, human

Topics

• Antigens, Neoplasm (analysis, genetics)
• Breast Neoplasms
• DNA Topoisomerases, Type II (genetics)
• DNA-Binding Proteins (genetics)
• Disease-Free Survival
• Female
• Humans
• Ki-67 Antigen (genetics, metabolism)
• Poly-ADP-Ribose Binding Proteins (genetics)
• Prognosis
• Receptor, ErbB-2 (metabolism)