Virchows Archiv

, Volume 474, Issue 2, pp 169–176 | Cite as

Digital quantification of KI-67 in breast cancer

  • María del Rosario Taco SanchezEmail author
  • Teresa Soler-Monsó
  • Anna Petit
  • Juan Azcarate
  • Alba Lasheras
  • Carmen Artal
  • Miguel Gil
  • Catalina Falo
  • María Jesús Pla
  • Xavier Matias-Guiu
Original Article


Ki-67 proliferative index (Ki-67) is a predictive and prognostic factor in breast cancer (BC). However, some international committees do not recommend its use in routine practice due to insufficient clinical evidence and lack of standardisation and assessment method reproducibility. Scoring of Ki-67 by digital pathology may contribute to overcome these drawbacks. We evaluated 136 core biopsies of BC patients and calculated the correlation of Ki-67 scored by two breast pathologists with two methods, eyeballing visual assessment (EB) on the microscope and digital image analysis (DI), both assessed from hot spot areas (HS) and the average between hot and cold spot areas (AVE). Good and higher correlation between pathologists was observed for HS using DI in comparison to EB (0.861 vs. 0.828). Correlation in HS with both methods was very similar in homogeneous tumours (0.869 vs. 0.866). Lower correlation was found in heterogeneous tumours if EB was used instead of DI (0.691 vs. 0.838). Good agreement with DI in AVE areas was observed in both homogenous and heterogeneous tumours (0.898 and 0.887). Concordance of tumour molecular profiles based on Ki-67 was better using DI in comparison to EB (Kappa index, 0.589 vs. 0675). Whereas EB and DI were alike in homogeneous tumour, DI improved agreement in heterogeneous tumours, particularly in AVE areas. Subgroup analysis for tumour grades also showed improvement of correlation by DI in AVE areas in all G1/G2/G3 groups. Digital pathology using AVE method can be useful for Ki-67 scoring in daily practice, especially in heterogeneous and G2 tumours, by a substantial improvement of agreement between observers and results accuracy.


Digital analysis Ki-67 Breast cancer Reproducibility Immunohistochemistry Prognosis 



We thank Xavier Pérez Martín (Clinical Research Unit, Catalan Oncology Institute) for the statistical analysis support. We also thank Sysmex España for technical support.

Ethical responsibilities of authors section

All authors contributed equally to the study design, results analysis and manuscript conception.

Compliance with ethical standards

The study was approved by the Ethics Committee of the hospital. The study was performed in compliance with The Code of Ethics of the World Medical Association (Declaration of Helsinki).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

428_2018_2481_MOESM1_ESM.docx (40 kb)
ESM 1 (DOCX 40 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • María del Rosario Taco Sanchez
    • 1
    Email author
  • Teresa Soler-Monsó
    • 1
    • 2
  • Anna Petit
    • 1
  • Juan Azcarate
    • 1
  • Alba Lasheras
    • 1
  • Carmen Artal
    • 1
  • Miguel Gil
    • 2
  • Catalina Falo
    • 2
  • María Jesús Pla
    • 3
  • Xavier Matias-Guiu
    • 4
  1. 1.Department of PathologyBellvitge University Hospital, IDIBELL, CIBERONCBarcelonaSpain
  2. 2.Catalan Breast Unit, Catalan Institute of OncologyICO L’Hospitalet de LlobregatBarcelonaSpain
  3. 3.Department of GynecologyBellvitge University Hospital, IDIBELL, IRBLLEIDA, CIBERONCBarcelonaSpain
  4. 4.Bellvitge University Hospital and Arnau de Vilanova University Hospital, IDIBELL, IRBLLEIDA, CIBERONCBarcelonaSpain

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