The prognostic significance of topoisomerase II alpha protein in early stage luminal breast cancer

Xin An,Zhongyu Yuan,Rongzhen Luo,Shusen Wang,Jiabin Lu,Yanxia Shi,Wenqi Jiang,Yanhua Yang,Qiufan Zheng,Tao Qin,Fei Xu

doi:10.1186/s12885-018-4170-7

Abstract

BackgroundTopoisomerase II alpha (TOP2A) protein has been shown to be a proliferation marker associated with tumor grade and Ki67 index. The prognostic effect of TOP2A seems different among different subtypes of breast cancer. The current study evaluated the prognostic impact of TOP2A protein on luminal breast cancer.MethodAltogether 434 stage I-II luminal breast cancer patients who underwent curative surgery in Sun Yat-Sen University Cancer Center between 2007 and 2009 were enrolled. TOP2A protein expression was assessed by immunohistochemistry. Clinical and pathological data were retrospectively collected.ResultWith a cut-off value of 30%, 127 (29.3%) patients were classified as TOP2A overexpression. TOP2A overexpression was associated with a higher tumor grade and Ki67 index. Patients with TOP2A high expression showed a significantly higher rate of distant metastasis and shorter distant metastasis free survival (DMFS) compared with patients with low TOP2A expression. The prognostic influence of TOP2A expression was more significant in years 5–8 after diagnosis, and more pronounced in stage II patients, luminal B disease, and patients treated with adjuvant endocrine therapy alone. Multivariate survival analysis revealed TOP2A overexpression was an independent fact for worse DMFS.ConclusionTOP2A protein showed a time dependent influence on prognosis in stage I-II luminal breast cancer, suggesting it might be a potential predictor of late recurrence for this group of patients.

Highlights

Topoisomerase II alpha (TOP2A) protein has been shown to be a proliferation marker associated with tumor grade and Ki67 index
TOP2A protein showed a time dependent influence on prognosis in stage I-II luminal breast cancer, suggesting it might be a potential predictor of late recurrence for this group of patients
We found the unfavourable impact of TOP2A overexpression on distant metastasis free survival (DMFS) was statistically significant in stage II disease (P = 0.025), luminal B patients (P = 0.046), and patients treated with adjuvant endocrine therapy alone without chemotherapy (P = 0.014) (Fig.. 3)

Summary

Introduction

Topoisomerase II alpha (TOP2A) protein has been shown to be a proliferation marker associated with tumor grade and Ki67 index. The prognostic effect of TOP2A seems different among different subtypes of breast cancer. Luminal breast cancer, defined by the presence of estrogen receptor(ER) and/or progesterone receptor (PgR) and absence of human epidermal growth factor receptor 2 (HER2), is the most common subtype of breast cancer. This subtype generally shows favorable survival, better response to endocrine therapy, and less benefit from chemotherapy [1, 2]. Extended gene expression profiling (GEP) has divided luminal breast cancer into A and B subtypes that improves prognostication and prediction of response to therapy [1, 7]. Quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) based multigene assays such as

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