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Research Papers:

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

Hideo Shigematsu _, Shinji Ozaki, Daisuke Yasui, Hideki Yamamoto, Junichi Zaitsu, Daiki Taniyama, Akihisa Saitou, Kazuya Kuraoka, Taizo Hirata and Kiyomi Taniyama

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Oncotarget. 2018; 9:26701-26710. https://doi.org/10.18632/oncotarget.25468

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Abstract

Hideo Shigematsu1, Shinji Ozaki1, Daisuke Yasui1, Hideki Yamamoto2, Junichi Zaitsu2, Daiki Taniyama2, Akihisa Saitou2, Kazuya Kuraoka2, Taizo Hirata3 and Kiyomi Taniyama4

1Department of Breast Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure-City, Hiroshima, Japan

2Department of Pathology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure-City, Hiroshima, Japan

3Department of Medical Oncology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure-City, Hiroshima, Japan

4National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure-City, Hiroshima, Japan

Correspondence to:

Hideo Shigematsu, email: [email protected]

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 (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.


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