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, Kiyomi Taniyama

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)26701-26710
Number of pages10
JournalOncotarget
Volume9
Issue number42
DOIs
Publication statusPublished - Jun 1 2018
Externally publishedYes

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Breast Neoplasms
Proteins
Therapeutics
DNA topoisomerase II alpha

Keywords

  • Breast cancer
  • Luminal B
  • Prognostic value
  • Topoisomerase IIA

ASJC Scopus subject areas

  • Oncology

Cite this

Overexpression of topoisomerase II alpha protein is a factor for poor prognosis in patients with luminal B breast cancer. / Shigematsu, Hideo; Ozaki, Shinji; Yasui, Daisuke; Yamamoto, Hideki; Zaitsu, Junichi; Taniyama, Daiki; Saitou, Akihisa; Kuraoka, Kazuya; Hirata, Taizo; Taniyama, Kiyomi.

In: Oncotarget, Vol. 9, No. 42, 01.06.2018, p. 26701-26710.

Research output: Contribution to journalArticle

Shigematsu, H, Ozaki, S, Yasui, D, Yamamoto, H, Zaitsu, J, Taniyama, D, Saitou, A, Kuraoka, K, Hirata, T & Taniyama, K 2018, 'Overexpression of topoisomerase II alpha protein is a factor for poor prognosis in patients with luminal B breast cancer', Oncotarget, vol. 9, no. 42, pp. 26701-26710. https://doi.org/10.18632/oncotarget.25468
Shigematsu, Hideo ; Ozaki, Shinji ; Yasui, Daisuke ; Yamamoto, Hideki ; Zaitsu, Junichi ; Taniyama, Daiki ; Saitou, Akihisa ; Kuraoka, Kazuya ; Hirata, Taizo ; Taniyama, Kiyomi. / Overexpression of topoisomerase II alpha protein is a factor for poor prognosis in patients with luminal B breast cancer. In: Oncotarget. 2018 ; Vol. 9, No. 42. pp. 26701-26710.
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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.",
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AU - Shigematsu, Hideo

AU - Ozaki, Shinji

AU - Yasui, Daisuke

AU - Yamamoto, Hideki

AU - Zaitsu, Junichi

AU - Taniyama, Daiki

AU - Saitou, Akihisa

AU - Kuraoka, Kazuya

AU - Hirata, Taizo

AU - Taniyama, Kiyomi

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N2 - 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.

AB - 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.

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KW - Luminal B

KW - Prognostic value

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