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


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 (?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.

SUBMITTER: Shigematsu H 

PROVIDER: S-EPMC6003555 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Shigematsu Hideo H   Ozaki Shinji S   Yasui Daisuke D   Yamamoto Hideki H   Zaitsu Junichi J   Taniyama Daiki D   Saitou Akihisa A   Kuraoka Kazuya K   Hirata Taizo T   Taniyama Kiyomi K  

Oncotarget 20180601 42


<h4>Background</h4>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.<h4>Results</h4>The frequencies of TOP2A overexpression and <i>TOP2A</i> amplified were 55.8% and 9.5%, respectively. TOP2A overexpression correlated strongly with non-luminal A subtype (χ<sup>2</sup>-test, <i>p <</i> 0.001). TOP2A overexpression was significantly associated with relapse-free survival i  ...[more]

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