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Prognostic implications of securin expression and sub-cellular localization in human breast cancer

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Abstract

Purpose

Securin belongs to a class of cell cycle regulators that prevent metaphase-to-anaphase transition until sister chromatid separation is complete. Evidence is accumulating that securin has a prognostic impact on a variety of malignancies but, thus far, the role and regulation of securin expression and its sub-cellular localization have not been systematically addressed in breast cancer.

Methods

In total 470 breast cancer specimens with follow-up data for up to 22 years were included. Immunohistochemical staining and immunofluorescence double-staining were performed for securin and its regulating proteins PTTG1IP, CDC20 and BUBR1. Prognostic associations were evaluated between the expression patterns of these proteins and established prognosticators of invasive breast cancer and patient survival.

Results

We found that a high fraction of securin expressing cancer cells predicted an unfavorable clinical outcome of the breast cancer patients (p < 0.001). Also in multivariate analyses, the fraction of securin expressing cancer cells served as an independent prognosticator of a poor survival (p < 0.0001). We also found that the sub-cellular localization of securin exhibited prognostic power, since cytoplasmic securin expression in the cancer cells appeared to be associated with aggressive breast cancer subtypes and high breast cancer-associated mortality rates (p = 0.003). Through immunofluorescence double-staining, we found that PTTG1IP, CDC20 and BUBR1 exhibited distinct patterns of co-expression with securin, suggesting a regulatory role in the metaphase-to-anaphase transition in human breast cancer cells. We also noted that a subgroup of triple-negative breast carcinomas exhibited deviant expression patterns for the proteins studied.

Conclusions

Our data indicate that securin expression may serve as a strong and independent prognosticator of breast cancer outcome and that a cytoplasmic localization of the protein may provide additional prognostic information, particularly in the biologically and clinically challenging subgroup of triple-negative breast carcinomas. The sub-cellular localization of securin appears to reflect the expression of PTTG1IP, CDC20 and BUBR1, which may participate in the regulation of securin activity and, ultimately, in the survival of breast cancer patients.

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Acknowledgments

We wish to thank Mrs. Sinikka Collanus for the help with histology and immunohistochemistry, and Mr. Jaakko Liippo for technical support with the photographs.

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Authors and Affiliations

  1. Department of Pathology and Forensic Medicine, University of Turku and Turku University Hospital, Kiinamyllynkatu 10, 20500, Turku, Finland

    N. Gurvits, H. Repo, K. Talvinen & P. Kronqvist

  2. Department of Biostatistics, University of Turku, Turku, Finland

    E. Löyttyniemi

  3. Department of Pathology, Central Finland Central Hospital, Jyväskylä, Finland

    M. Nykänen, J. Anttinen & T. Kuopio

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  1. N. Gurvits
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Correspondence to N. Gurvits.

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All procedures performed involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal informed consent is not required.

Funding

This study was funded by the Turku University Hospital and the Research Foundation of Clinical Chemistry (Kliinisen kemian tutkimussäätiö), Finland.

Conflict of interest

The authors declare that they have no conflict of interest.

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Gurvits, N., Repo, H., Löyttyniemi, E. et al. Prognostic implications of securin expression and sub-cellular localization in human breast cancer. Cell Oncol. 39, 319–331 (2016). https://doi.org/10.1007/s13402-016-0277-5

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  • DOI: https://doi.org/10.1007/s13402-016-0277-5

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