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

Publikation: Bidrag til tidsskriftKonferenceartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftActa Oncologica
Vol/bind57
Udgave nummer1
Sider (fra-til)83-89
ISSN0284-186X
DOI
StatusUdgivet - jan. 2018
Begivenhed16th Acta Oncologica Symposium - Aarhus , Danmark
Varighed: 18. jan. 201819. jan. 2018

Konference

Konference16th Acta Oncologica Symposium
LandDanmark
ByAarhus
Periode18/01/201819/01/2018

Fingeraftryk

Pathology
Observer Variation
Observation
Guidelines

Citer dette

Laenkholm, Anne-Vibeke ; Grabau, Dorthe ; Møller Talman, Maj-Lis ; Balslev, Eva ; Bak Jylling, Anne Marie ; Tabor, Tomasz Piotr ; Johansen, Morten ; Brügmann, Anja ; Lelkaitis, Giedrius ; Di Caterino, Tina ; Mygind, Henrik ; Poulsen, Thomas ; Mertz, Henrik ; Søndergaard, Gorm ; Bruun Rasmussen, Birgitte. / 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). I: Acta Oncologica. 2018 ; Bind 57, Nr. 1. s. 83-89.
@inproceedings{e0221a8bae264ac6990068c521b9cfe7,
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 {M{\o}ller Talman}, Maj-Lis 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 {Bruun Rasmussen}, Birgitte",
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month = "1",
doi = "10.1080/0284186X.2017.1404127",
language = "English",
volume = "57",
pages = "83--89",
journal = "Acta Oncologica",
issn = "0284-186X",
publisher = "Taylor & Francis",
number = "1",

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Laenkholm, A-V, Grabau, D, Møller Talman, M-L, Balslev, E, Bak Jylling, AM, Tabor, TP, Johansen, M, Brügmann, A, Lelkaitis, G, Di Caterino, T, Mygind, H, Poulsen, T, Mertz, H, Søndergaard, G & Bruun Rasmussen, 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, bind 57, nr. 1, s. 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; Møller Talman, Maj-Lis; Balslev, Eva; Bak Jylling, Anne Marie; Tabor, Tomasz Piotr; Johansen, Morten; Brügmann, Anja; Lelkaitis, Giedrius; Di Caterino, Tina; Mygind, Henrik; Poulsen, Thomas; Mertz, Henrik; Søndergaard, Gorm; Bruun Rasmussen, Birgitte.

I: Acta Oncologica, Bind 57, Nr. 1, 01.2018, s. 83-89.

Publikation: Bidrag til tidsskriftKonferenceartikelForskningpeer review

TY - GEN

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 - Møller Talman, Maj-Lis

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 - Bruun Rasmussen, Birgitte

PY - 2018/1

Y1 - 2018/1

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 - Conference article

VL - 57

SP - 83

EP - 89

JO - Acta Oncologica

JF - Acta Oncologica

SN - 0284-186X

IS - 1

ER -