Automated Ki67 hot-spot detection and analysis Mieke Zwager MD, - - PowerPoint PPT Presentation

automated ki67 hot spot detection and analysis
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Automated Ki67 hot-spot detection and analysis Mieke Zwager MD, - - PowerPoint PPT Presentation

Automated Ki67 hot-spot detection and analysis Mieke Zwager MD, PhD student Department of Pathology University of Groningen, University Medical Center Groningen The Netherlands Background Ki67 Nuclear protein Expressed during cell


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Automated Ki67 hot-spot detection and analysis

Mieke Zwager

MD, PhD student Department of Pathology University of Groningen, University Medical Center Groningen The Netherlands

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Background

Ki67

  • Nuclear protein
  • Expressed during cell cycle
  • Prognostic and predictive in breast cancer

G1 M S G2 G0 Ki67 low Ki67 high

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Background

Standardised manual Ki67 hot-spot scoring

  • Select one high-power field with highest staining rate
  • Count up to 500 cells
  • Type-writer pattern
  • Median scoring time: 6 minutes (4-8)

S.C.Y. Leung et al. Analytical validation of a standardised scoring protocol for Ki67 immunohistochemistry on breast cancer excision whole sections: an international multicentre collaboration. Histopathology 2019: 75;225-235.

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Background

Hot-spot scoring

  • Visual identification is difficult
  • Labour-intensive
  • Inter- and intra-observer variability
  • Inter-observer reproducibility/ICC of 0.8

S.C.Y. Leung et al. Analytical validationof a standardised scoring protocol for Ki67 immunohistochemistry on breast cancer excision whole sections: an international multicentre collaboration. Histopathology 2019: 75;225-235.

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Background & Objective

Digital image analysis

  • Automated detection and scoring
  • Standardised and reproducible

Objective

  • Compare manual Ki67 hot-spot scoring and

detection with digital image analysis (DIA)

Koopman T. et al. Digital image analysis of Ki67 proliferation index in breast cancer using virtual dual staining on whole tissue sections: clinical validation and inter-platform agreement. Breast Cancer Res Treat. 2018; 169:33-42.

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Methods

102 breast carcinomas Manual hot-spot detection and scoring

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Methods

Automated hot-spot detection and scoring DIA manual hot-spot Manual hot-spot detection and scoring

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Automated hot-spot selection and analysis

  • 1. Tumor

identification

  • 2. DCIS vs.

invasive tumor discrimination

  • 3. Ki67

quantification

  • 4. Heat map

creation

  • 5. Hot spot

identification

  • 6. Ki67

quantification within hot spot

VirtualDoubleStaining™

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Manual Ki67 hot-spot correlation is suboptimal

R² = 0,78

10 20 30 40 50 60 70 80 90 10 20 30 40 50 60 70 80 90 100 Manual Scores Observer 2 Manual Scores Observer 1

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Manual and DIA scores of the manual ROIs strongly correlate

R² = 0,90

10 20 30 40 50 60 70 80 90 100 10 20 30 40 50 60 70 80 90 100 Image Analysis Manual Scores

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Automated Ki67 hot-spot analysis leads to higher proliferation indices

5 10 15 20 25 30 35 40 45 Observer 1 Observer 2 DIA

Mean Ki67 hot-spot score

Mean Ki67 hot-spot score

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Conclusion

Automated Ki67 hot-spot detection and analysis is a reliable method that leads to higher hot-spot Ki67 proliferation indices

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Acknowledgments

UMCG/UG

  • Dr. Bert van der Vegt
  • Dr. Timco Koopman
  • Henk Buikema

Visiopharm

  • Dr. Henrik Klingberg
  • Dzenita Omanovic
  • Dr. Andreas Schønau