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Expression of SIRT1 and apoptosis-related proteins is predictive for lymph node metastasis and disease-free survival in luminal A breast cancer

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Abstract

Luminal A breast cancer can present with early, unexpected lymph node metastasis, and sentinel lymph node biopsy has been reported false negative in some cases. We aimed to construct a biomarker-based model that predicts lymph node metastasis in luminal A breast cancer, using expression of silent mating type information regulation 2 homolog 1 (SIRT1) and apoptosis-related factors, which are known to be closely related. We selected tissue samples of 278 cases of luminal A invasive ductal carcinoma, constructed tissue microarrays, and performed immunohistochemical staining for SIRT1 and four apoptosis-related proteins. In constructing the best predictive model for lymph node metastasis, six clinicopathological parameters and five molecular markers were considered. Independent factors predictive of lymph node metastasis were pT stage (OR 1.829, p = 0.027), lymphovascular invasion (OR 4.128, p < 0.001), and decreased expression of caspase-3 (OR 0.535, p = 0.034) and of SIRT1 (OR 0.526, p = 0.053). A combination nuclear grade, lymphovascular invasion, increased B-cell lymphoma 2 (Bcl-2) expression, and reduced expression of caspase-3 and of SIRT1 yielded the strongest predictive performance for lymph node metastasis with an area under the curve (AUC) of 0.696. This combination was also predictive of shortened disease-free survival (73.1 vs. 67.7 months, p = 0.003). Our data support a role of SIRT1 protein as tumor suppressor in luminal A breast cancer, in association with apoptosis-related proteins. Our model based upon a combination of these biomarkers is expected to increase accuracy of prediction of lymph node metastasis in luminal A breast cancer. This might serve as a valuable tool in determining the optimal surgical strategy in breast cancer patients.

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Acknowledgments

This study was supported by Grant No. 04-2013-0840 from Seoul National University Hospital Research Fund.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Pathology, Seoul National University Hospital, Seoul, Korea

    Hyojin Kim, In Ae Park, Yul Ri Chung & Han Suk Ryu

  2. Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

    Kyung-Hun Lee & Seock-Ah Im

  3. Department of Surgery, Seoul National University Hospital, Seoul, Korea

    Dong-Young Noh, Wonshik Han & Hyeong-Gon Moon

  4. Department of Pathology, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea

    Yoon Yang Jung

Authors
  1. Hyojin Kim
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  2. Kyung-Hun Lee
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  3. In Ae Park
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  10. Han Suk Ryu
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Corresponding authors

Correspondence to Seock-Ah Im or Han Suk Ryu.

Additional information

Han Suk Ryu and Seock-Ah Im evenly contributed to this work as co-corresponding authors.

Hyojin Kim and Kyung-Hun Lee evenly contributed to this work as co-first authors.

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Supplementary Fig. 1

(A&B) Comparison of disease-free survival for low and high risk groups according to the use of postoperative adjuvant chemotherapy. (C&D) Comparison of disease-free survival for low and high risk groups according to the use of postoperative adjuvant hormone receptor blockers (JPEG 638 kb)

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Kim, H., Lee, KH., Park, I.A. et al. Expression of SIRT1 and apoptosis-related proteins is predictive for lymph node metastasis and disease-free survival in luminal A breast cancer. Virchows Arch 467, 563–570 (2015). https://doi.org/10.1007/s00428-015-1815-7

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  • DOI: https://doi.org/10.1007/s00428-015-1815-7

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