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Proliferation-associated miRNAs-494, -205, -21 and -126 detected by in situ hybridization: expression and prognostic potential in breast carcinoma patients

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

To visualize by in situ hybridization (ISH) the levels of a set of proliferation-associated miRNAs and to evaluate their impact and clinical applicability in prognostication of invasive breast carcinoma.

Methods

Tissue specimen from breast carcinoma patients were investigated for miRNAs-494, -205, -21 and -126. Prognostic associations for levels of miRNAs were analyzed based on complete clinical data and up to 22.5-year follow-up of the patient material (n = 285). For detection of the miRNAs, an automated sensitive protocol applying in situ hybridization was developed.

Results

MiRNA-494 indicated prognostic value for patients with invasive breast carcinoma. Among node-negative disease reduced level of miRNA-494 predicted 8.5-fold risk of breast cancer death (p = 0.04). Altered levels and expression patterns of the studied miRNAs were observed in breast carcinomas as compared to benign breast tissue.

Conclusions

The present paper reports for the first time on the prognostic value of miRNA-494 in invasive breast cancer. Particularly, detection of miRNA-494 could benefit patients with node-negative breast cancer in identifying subgroups with aggressive disease. Based on our experience, the developed automatic ISH method to visualize altered levels of miRNAs-494, -205, -21 and -126 could be applied to routine pathology diagnostics providing that conditions of tissue treatment, especially fixation delays, are managed.

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Acknowledgements

The authors thank Mrs. Sinikka Collanus, PhD Markus Peurla and Mr. Jaakko Liippo, Institute of Biomedicine, University of Turku, Turku, Finland.

Funding

The study was supported by grants from Cancer Society of South-West Finland, Foundation of Finska Läkaresällskapet and Turku University Hospital.

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Authors and Affiliations

  1. Department of Pathology, Turku University Hospital, and Institute of Biomedicine, University of Turku, Turku, Finland

    Natalia Gurvits, Tuomo-Artturi Autere, Heli Repo, Pauliina Kronqvist & Kati Talvinen

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

    Marjukka Nykänen

  3. Biological and Environmental Science, University of Jyväskylä, Jyväskylä, Finland

    Teijo Kuopio

  4. Department of Pathology, Central Finland Health Care District, Jyväskylä, Finland

    Teijo Kuopio

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  1. Natalia Gurvits
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  2. Tuomo-Artturi Autere
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  4. Marjukka Nykänen
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Correspondence to Natalia Gurvits.

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The authors declare that they have no conflict of interest.

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Informed consent was obtained from all individual participants included in the study.

Ethical approval

All procedures performed in studies 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. The work has been approved by the ethics committees of Turku University Hospital and Central Hospital of Central Finland, Turku, Finland (permit numbers 0286/2002, 7765-2002 and AB159859). All patient material has been obtained from archives of biobanks and includes written consent from patients obtained in accordance to the ethics permits and the Finnish Biobank Act (688/2012).

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Gurvits, N., Autere, TA., Repo, H. et al. Proliferation-associated miRNAs-494, -205, -21 and -126 detected by in situ hybridization: expression and prognostic potential in breast carcinoma patients. J Cancer Res Clin Oncol 144, 657–666 (2018). https://doi.org/10.1007/s00432-018-2586-8

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