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

// Hideo Shigematsu 1 , Shinji Ozaki 1 , Daisuke Yasui 1 , Hideki Yamamoto 2 , Junichi Zaitsu 2 , Daiki Taniyama 2 , Akihisa Saitou 2 , Kazuya Kuraoka 2 , Taizo Hirata 3 and Kiyomi Taniyama 4 1 Department of Breast Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure-City, Hiroshima, Japan 2 Department of Pathology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure-City, Hiroshima, Japan 3 Department of Medical Oncology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure-City, Hiroshima, Japan 4 National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure-City, Hiroshima, Japan Correspondence to: Hideo Shigematsu, email: shigematu1330@yahoo.co.jp Keywords: breast cancer; topoisomerase IIA; prognostic value; luminal B Received: April 04, 2018 Accepted: May 05, 2018 Published: June 01, 2018 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 non-luminal A subtype (χ 2 -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.