An inter-observer Ki67 reproducibility study applying two different assessment methods: on behalf of the Danish Scientific Committee of Pathology, Danish breast cancer cooperative group (DBCG)

Anne-Vibeke Laenkholm; Dorthe Grabau; Maj-Lis Møller Talman; Eva Balslev; Anne Marie Bak Jylling; Tomasz Piotr Tabor; Morten Johansen; Anja Brügmann; Giedrius Lelkaitis; Tina Di Caterino; Henrik Mygind; Thomas Poulsen; Henrik Mertz; Gorm Søndergaard; Birgitte Bruun Rasmussen

doi:10.1080/0284186x.2017.1404127

An inter-observer Ki67 reproducibility study applying two different assessment methods: on behalf of the Danish Scientific Committee of Pathology, Danish breast cancer cooperative group (DBCG)

Anne-Vibeke Laenkholm, Dorthe Grabau, Maj-Lis Møller Talman, Eva Balslev, Anne Marie Bak Jylling, Tomasz Piotr Tabor, Morten Johansen, Anja Brügmann, Giedrius Lelkaitis, Tina Di Caterino, Henrik Mygind, Thomas Poulsen, Henrik Mertz, Gorm Søndergaard, Birgitte Bruun Rasmussen

Department of Clinical Medicine

19 Citations (Scopus)

Abstract

INTRODUCTION: In 2011, the St. Gallen Consensus Conference introduced the use of pathology to define the intrinsic breast cancer subtypes by application of immunohistochemical (IHC) surrogate markers ER, PR, HER2 and Ki67 with a specified Ki67 cutoff (>14%) for luminal B-like definition. Reports concerning impaired reproducibility of Ki67 estimation and threshold inconsistency led to the initiation of this quality assurance study (2013-2015). The aim of the study was to investigate inter-observer variation for Ki67 estimation in malignant breast tumors by two different quantification methods (assessment method and count method) including measure of agreement between methods.

MATERIAL AND METHODS: Fourteen experienced breast pathologists from 12 pathology departments evaluated 118 slides from a consecutive series of malignant breast tumors. The staining interpretation was performed according to both the Danish and Swedish guidelines. Reproducibility was quantified by intra-class correlation coefficient (ICC) and Lights Kappa with dichotomization of observations at the larger than (>) 20% threshold. The agreement between observations by the two quantification methods was evaluated by Bland-Altman plot.

RESULTS: For the fourteen raters the median ranged from 20% to 40% by the assessment method and from 22.5% to 36.5% by the count method. Light's Kappa was 0.664 for observation by the assessment method and 0.649 by the count method. The ICC was 0.82 (95% CI: 0.77-0.86) by the assessment method vs. 0.84 (95% CI: 0.80-0.87) by the count method.

CONCLUSION: Although the study in general showed a moderate to good inter-observer agreement according to both ICC and Lights Kappa, still major discrepancies were identified in especially the mid-range of observations. Consequently, for now Ki67 estimation is not implemented in the DBCG treatment algorithm.

Original language	English
Journal	Acta Oncologica
Volume	57
Issue number	1
Pages (from-to)	83-89
Number of pages	7
ISSN	0284-186X
DOIs	https://doi.org/10.1080/0284186x.2017.1404127
Publication status	Published - 2 Jan 2018

Keywords

Biomarkers/metabolism
Breast Neoplasms/pathology
Consensus Development Conferences as Topic
Denmark
Female
Humans
Immunohistochemistry/standards
Ki-67 Antigen/metabolism
Pathology, Clinical/standards
Practice Guidelines as Topic
Reproducibility of Results
Staining and Labeling/methods

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Laenkholm, A-V., Grabau, D., Talman, M-L. M., Balslev, E., Bak Jylling, A. M., Tabor, T. P., Johansen, M., Brügmann, A., Lelkaitis, G., Di Caterino, T., Mygind, H., Poulsen, T., Mertz, H., Søndergaard, G., & Rasmussen, B. B. (2018). An inter-observer Ki67 reproducibility study applying two different assessment methods: on behalf of the Danish Scientific Committee of Pathology, Danish breast cancer cooperative group (DBCG). Acta Oncologica, 57(1), 83-89. https://doi.org/10.1080/0284186x.2017.1404127

An inter-observer Ki67 reproducibility study applying two different assessment methods : on behalf of the Danish Scientific Committee of Pathology, Danish breast cancer cooperative group (DBCG). / Laenkholm, Anne-Vibeke; Grabau, Dorthe; Talman, Maj-Lis Møller et al.

In: Acta Oncologica, Vol. 57, No. 1, 02.01.2018, p. 83-89.

Research output: Contribution to journal › Journal article › Research › peer-review

Laenkholm, A-V, Grabau, D, Talman, M-LM, Balslev, E, Bak Jylling, AM, Tabor, TP, Johansen, M, Brügmann, A, Lelkaitis, G, Di Caterino, T, Mygind, H, Poulsen, T, Mertz, H, Søndergaard, G & Rasmussen, BB 2018, 'An inter-observer Ki67 reproducibility study applying two different assessment methods: on behalf of the Danish Scientific Committee of Pathology, Danish breast cancer cooperative group (DBCG)', Acta Oncologica, vol. 57, no. 1, pp. 83-89. https://doi.org/10.1080/0284186x.2017.1404127

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title = "An inter-observer Ki67 reproducibility study applying two different assessment methods: on behalf of the Danish Scientific Committee of Pathology, Danish breast cancer cooperative group (DBCG)",

abstract = "INTRODUCTION: In 2011, the St. Gallen Consensus Conference introduced the use of pathology to define the intrinsic breast cancer subtypes by application of immunohistochemical (IHC) surrogate markers ER, PR, HER2 and Ki67 with a specified Ki67 cutoff (>14%) for luminal B-like definition. Reports concerning impaired reproducibility of Ki67 estimation and threshold inconsistency led to the initiation of this quality assurance study (2013-2015). The aim of the study was to investigate inter-observer variation for Ki67 estimation in malignant breast tumors by two different quantification methods (assessment method and count method) including measure of agreement between methods.MATERIAL AND METHODS: Fourteen experienced breast pathologists from 12 pathology departments evaluated 118 slides from a consecutive series of malignant breast tumors. The staining interpretation was performed according to both the Danish and Swedish guidelines. Reproducibility was quantified by intra-class correlation coefficient (ICC) and Lights Kappa with dichotomization of observations at the larger than (>) 20% threshold. The agreement between observations by the two quantification methods was evaluated by Bland-Altman plot.RESULTS: For the fourteen raters the median ranged from 20% to 40% by the assessment method and from 22.5% to 36.5% by the count method. Light's Kappa was 0.664 for observation by the assessment method and 0.649 by the count method. The ICC was 0.82 (95% CI: 0.77-0.86) by the assessment method vs. 0.84 (95% CI: 0.80-0.87) by the count method.CONCLUSION: Although the study in general showed a moderate to good inter-observer agreement according to both ICC and Lights Kappa, still major discrepancies were identified in especially the mid-range of observations. Consequently, for now Ki67 estimation is not implemented in the DBCG treatment algorithm.",

keywords = "Biomarkers/metabolism, Breast Neoplasms/pathology, Consensus Development Conferences as Topic, Denmark, Female, Humans, Immunohistochemistry/standards, Ki-67 Antigen/metabolism, Pathology, Clinical/standards, Practice Guidelines as Topic, Reproducibility of Results, Staining and Labeling/methods",

author = "Anne-Vibeke Laenkholm and Dorthe Grabau and Talman, {Maj-Lis M{\o}ller} and Eva Balslev and {Bak Jylling}, {Anne Marie} and Tabor, {Tomasz Piotr} and Morten Johansen and Anja Br{\"u}gmann and Giedrius Lelkaitis and {Di Caterino}, Tina and Henrik Mygind and Thomas Poulsen and Henrik Mertz and Gorm S{\o}ndergaard and Rasmussen, {Birgitte Bruun}",

note = "Volume 57, 2018 - Issue 1: Papers at the occasion of the 40-years anniversary of DBCG – the Danish Breast Cancer Cooperative Group and the 16th Acta Oncologica Symposium, Aarhus, Denmark - January 18-19, 2018 ",

year = "2018",

month = jan,

day = "2",

doi = "10.1080/0284186x.2017.1404127",

language = "English",

volume = "57",

pages = "83--89",

journal = "Acta Oncologica, Supplement",

issn = "1100-1704",

publisher = "Taylor & Francis",

number = "1",

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TY - JOUR

T1 - An inter-observer Ki67 reproducibility study applying two different assessment methods

T2 - on behalf of the Danish Scientific Committee of Pathology, Danish breast cancer cooperative group (DBCG)

AU - Laenkholm, Anne-Vibeke

AU - Grabau, Dorthe

AU - Talman, Maj-Lis Møller

AU - Balslev, Eva

AU - Bak Jylling, Anne Marie

AU - Tabor, Tomasz Piotr

AU - Johansen, Morten

AU - Brügmann, Anja

AU - Lelkaitis, Giedrius

AU - Di Caterino, Tina

AU - Mygind, Henrik

AU - Poulsen, Thomas

AU - Mertz, Henrik

AU - Søndergaard, Gorm

AU - Rasmussen, Birgitte Bruun

N1 - Volume 57, 2018 - Issue 1: Papers at the occasion of the 40-years anniversary of DBCG – the Danish Breast Cancer Cooperative Group and the 16th Acta Oncologica Symposium, Aarhus, Denmark - January 18-19, 2018

PY - 2018/1/2

Y1 - 2018/1/2

N2 - INTRODUCTION: In 2011, the St. Gallen Consensus Conference introduced the use of pathology to define the intrinsic breast cancer subtypes by application of immunohistochemical (IHC) surrogate markers ER, PR, HER2 and Ki67 with a specified Ki67 cutoff (>14%) for luminal B-like definition. Reports concerning impaired reproducibility of Ki67 estimation and threshold inconsistency led to the initiation of this quality assurance study (2013-2015). The aim of the study was to investigate inter-observer variation for Ki67 estimation in malignant breast tumors by two different quantification methods (assessment method and count method) including measure of agreement between methods.MATERIAL AND METHODS: Fourteen experienced breast pathologists from 12 pathology departments evaluated 118 slides from a consecutive series of malignant breast tumors. The staining interpretation was performed according to both the Danish and Swedish guidelines. Reproducibility was quantified by intra-class correlation coefficient (ICC) and Lights Kappa with dichotomization of observations at the larger than (>) 20% threshold. The agreement between observations by the two quantification methods was evaluated by Bland-Altman plot.RESULTS: For the fourteen raters the median ranged from 20% to 40% by the assessment method and from 22.5% to 36.5% by the count method. Light's Kappa was 0.664 for observation by the assessment method and 0.649 by the count method. The ICC was 0.82 (95% CI: 0.77-0.86) by the assessment method vs. 0.84 (95% CI: 0.80-0.87) by the count method.CONCLUSION: Although the study in general showed a moderate to good inter-observer agreement according to both ICC and Lights Kappa, still major discrepancies were identified in especially the mid-range of observations. Consequently, for now Ki67 estimation is not implemented in the DBCG treatment algorithm.

AB - INTRODUCTION: In 2011, the St. Gallen Consensus Conference introduced the use of pathology to define the intrinsic breast cancer subtypes by application of immunohistochemical (IHC) surrogate markers ER, PR, HER2 and Ki67 with a specified Ki67 cutoff (>14%) for luminal B-like definition. Reports concerning impaired reproducibility of Ki67 estimation and threshold inconsistency led to the initiation of this quality assurance study (2013-2015). The aim of the study was to investigate inter-observer variation for Ki67 estimation in malignant breast tumors by two different quantification methods (assessment method and count method) including measure of agreement between methods.MATERIAL AND METHODS: Fourteen experienced breast pathologists from 12 pathology departments evaluated 118 slides from a consecutive series of malignant breast tumors. The staining interpretation was performed according to both the Danish and Swedish guidelines. Reproducibility was quantified by intra-class correlation coefficient (ICC) and Lights Kappa with dichotomization of observations at the larger than (>) 20% threshold. The agreement between observations by the two quantification methods was evaluated by Bland-Altman plot.RESULTS: For the fourteen raters the median ranged from 20% to 40% by the assessment method and from 22.5% to 36.5% by the count method. Light's Kappa was 0.664 for observation by the assessment method and 0.649 by the count method. The ICC was 0.82 (95% CI: 0.77-0.86) by the assessment method vs. 0.84 (95% CI: 0.80-0.87) by the count method.CONCLUSION: Although the study in general showed a moderate to good inter-observer agreement according to both ICC and Lights Kappa, still major discrepancies were identified in especially the mid-range of observations. Consequently, for now Ki67 estimation is not implemented in the DBCG treatment algorithm.

KW - Biomarkers/metabolism

KW - Breast Neoplasms/pathology

KW - Consensus Development Conferences as Topic

KW - Denmark

KW - Female

KW - Humans

KW - Immunohistochemistry/standards

KW - Ki-67 Antigen/metabolism

KW - Pathology, Clinical/standards

KW - Practice Guidelines as Topic

KW - Reproducibility of Results

KW - Staining and Labeling/methods

U2 - 10.1080/0284186x.2017.1404127

DO - 10.1080/0284186x.2017.1404127

M3 - Journal article

C2 - 29202622

SN - 1100-1704

VL - 57

SP - 83

EP - 89

JO - Acta Oncologica, Supplement

JF - Acta Oncologica, Supplement

IS - 1

ER -

An inter-observer Ki67 reproducibility study applying two different assessment methods: on behalf of the Danish Scientific Committee of Pathology, Danish breast cancer cooperative group (DBCG)

Abstract

Keywords

UN SDGs

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