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The results of the quantitative evaluation of LI Ki67 by the open and commercial software for automatic image analysis in invasive breast carcinomas Bilbao, 2018 Vladimir Kushnarev, trainee of pathology department of N.N Petrov Cancer Research Center
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The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

Aug 29, 2019

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Page 1: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

The results of the quantitative evaluation of LI

Ki67 by the open and commercial software for

automatic image analysis in invasive breast

carcinomas

Bilbao, 2018

Vladimir Kushnarev,

trainee of pathology department of

N.N Petrov Cancer Research Center

Page 2: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

I have no actual or potential conflict

of interest in relation to this

presentation

Disclosure

Page 3: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

Surrogate molecular classification of breast carcinoma

Page 4: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

Surrogate molecular classification of breast carcinoma

Page 5: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

Breast Cancer

Index®

EndoPredict®

(EPclin®)

MammaPrint®

Oncotype DX®

Prosigna®

pT1a-b pN0 ER+ PR+ HER2-

low Ki67 and low grade

Surrogate molecular classification of breast carcinoma

Page 6: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

14% and 20% Ki67 - cut-off according to

recommendation

Problem of reproducibility in:

- preanalytical step

- analytical step

- postanalytical step

What is optimal cut-off for Ki67? Old story

Page 7: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

Ki-67 score is defined as the percentage of total number of tumour cells with

nuclear staining

Factors which influence on postanalytical step:

- Image analysis methods for Ki67 remain to be proven for

use in clinical practice.

- Lack of consensus about which area of the tumour

should be assessed

Modern interpretation of old story. What we can do?

Page 8: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

How to count?

Page 9: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

How to count?

Page 10: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

Digital Image Analysis

What we can do:

- standardization

- deep learning and pattern analysis

- big data

- high speed

How to count?

Page 11: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

How to count?

Page 12: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

Aim

To find out the possibilities of digital image analysis for the

quantitative evaluation of the expression of the Ki67 protein in

tumor cells

Page 13: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

How to count? Software for IHC assessment

Commercial and free software

Page 14: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

How to count?

Page 15: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

Open source and/or commercial software for IHC

assessment

Page 16: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

Design of experiment - 1 slide, same zone

Outcome: ICC - intraclass correlation

Expert 1 Software

Quant Cell

104 cases of NST breast carcinoma, ER+, HER2-

Expert 2 Software

QuPath

Software

Density Quant

Page 17: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

Detection of Ki67 zones - more than 1 mm2

Алгоритм определения плотности

опухолевых клеток

Алгоритм выделения зон опухолевых клеток

Page 18: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and
Page 19: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and
Page 20: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and
Page 21: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

Results

Page 22: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

Statistics method QuPath/ CellQuant Qupath/DensityQuant

r, Spearman 0.96 0.93

Intraclass coefficient, ICC 0.92 0.96

Results

Statistics method Qupath/Expert 1 Qupath/Expert 2

r, Spearman 0.90 0.90

Intraclass coefficient, ICC 0.85 0.88

Page 23: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

Data concordance of Ki67 skewness

Page 24: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

Take home message

The of LI Ki67 values obtained by the CD

module of freeware software showed a

strong correlation with the commercial

software of NQ module, as well as the

pathologist.

Free software QuPath can serve as a tool

for increasing the reproducibility of the

Ki67 proliferative activity index and

compete with commercial software for

image analysis.

Page 25: The results of the quantitative ... - esp-congress.org · Breast Cancer Index® EndoPredict® (EPclin®) MammaPrint® Oncotype DX® Prosigna® pT1a-b pN0 ER+ PR+ HER2-low Ki67 and

Thank you for your attention!