An international study to increase concordance in Ki67 scoring

Mei-Yin Polley, Samuel C.Y. Leung, Dongxia Gao, Mauro G. Mastropasqua, Lila A. Zabaglo, John M.S. Bartlett, Lisa M. Mcshane, Rebecca A. Enos, Sunil S. Badve, Anita L. Bane, Signe Borgquist, Susan Fineberg, Ming Gang Lin, Allen M. Gown, Dorthe Grabau, Carolina Gutierrez, Judith C. Hugh, Takuya Moriya, Yasuyo Ohi, C. Kent OsborneFrédérique M. Penault-Llorca, Tammy Piper, Peggy L. Porter, Takashi Sakatani, Roberto Salgado, Jane Starczynski, Anne Vibeke Lænkholm, Giuseppe Viale, Mitch Dowsett, Daniel F. Hayes, Torsten O. Nielsen

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Although an important biomarker in breast cancer, Ki67 lacks scoring standardization, which has limited its clinical use. Our previous study found variability when laboratories used their own scoring methods on centrally stained tissue microarray slides. In this current study, 16 laboratories from eight countries calibrated to a specific Ki67 scoring method and then scored 50 centrally MIB-1 stained tissue microarray cases. Simple instructions prescribed scoring pattern and staining thresholds for determination of the percentage of stained tumor cells. To calibrate, laboratories scored 18 'training' and 'test' web-based images. Software tracked object selection and scoring. Success for the calibration was prespecified as Root Mean Square Error of scores compared with reference <0.6 and Maximum Absolute Deviation from reference <1.0 (log2-transformed data). Prespecified success criteria for tissue microarray scoring required intraclass correlation significantly >0.70 but aiming for observed intraclass correlation ≥0.90. Laboratory performance showed non-significant but promising trends of improvement through the calibration exercise (mean Root Mean Square Error decreased from 0.6 to 0.4, Maximum Absolute Deviation from 1.6 to 0.9; paired t-test: P=0.07 for Root Mean Square Error, 0.06 for Maximum Absolute Deviation). For tissue microarray scoring, the intraclass correlation estimate was 0.94 (95% credible interval: 0.90-0.97), markedly and significantly >0.70, the prespecified minimum target for success. Some discrepancies persisted, including around clinically relevant cutoffs. After calibrating to a common scoring method via a web-based tool, laboratories can achieve high inter-laboratory reproducibility in Ki67 scoring on centrally stained tissue microarray slides. Although these data are potentially encouraging, suggesting that it may be possible to standardize scoring of Ki67 among pathology laboratories, clinically important discrepancies persist. Before this biomarker could be recommended for clinical use, future research will need to extend this approach to biopsies and whole sections, account for staining variability, and link to outcomes.

Original languageEnglish (US)
Pages (from-to)778-786
Number of pages9
JournalModern Pathology
Volume28
Issue number6
DOIs
StatePublished - Jun 1 2015
Externally publishedYes

Fingerprint

Research Design
Calibration
Biomarkers
Staining and Labeling
Software
Pathology
Breast Neoplasms
Biopsy
Neoplasms

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Polley, M-Y., Leung, S. C. Y., Gao, D., Mastropasqua, M. G., Zabaglo, L. A., Bartlett, J. M. S., ... Nielsen, T. O. (2015). An international study to increase concordance in Ki67 scoring. Modern Pathology, 28(6), 778-786. https://doi.org/10.1038/modpathol.2015.38

An international study to increase concordance in Ki67 scoring. / Polley, Mei-Yin; Leung, Samuel C.Y.; Gao, Dongxia; Mastropasqua, Mauro G.; Zabaglo, Lila A.; Bartlett, John M.S.; Mcshane, Lisa M.; Enos, Rebecca A.; Badve, Sunil S.; Bane, Anita L.; Borgquist, Signe; Fineberg, Susan; Lin, Ming Gang; Gown, Allen M.; Grabau, Dorthe; Gutierrez, Carolina; Hugh, Judith C.; Moriya, Takuya; Ohi, Yasuyo; Osborne, C. Kent; Penault-Llorca, Frédérique M.; Piper, Tammy; Porter, Peggy L.; Sakatani, Takashi; Salgado, Roberto; Starczynski, Jane; Lænkholm, Anne Vibeke; Viale, Giuseppe; Dowsett, Mitch; Hayes, Daniel F.; Nielsen, Torsten O.

In: Modern Pathology, Vol. 28, No. 6, 01.06.2015, p. 778-786.

Research output: Contribution to journalArticle

Polley, M-Y, Leung, SCY, Gao, D, Mastropasqua, MG, Zabaglo, LA, Bartlett, JMS, Mcshane, LM, Enos, RA, Badve, SS, Bane, AL, Borgquist, S, Fineberg, S, Lin, MG, Gown, AM, Grabau, D, Gutierrez, C, Hugh, JC, Moriya, T, Ohi, Y, Osborne, CK, Penault-Llorca, FM, Piper, T, Porter, PL, Sakatani, T, Salgado, R, Starczynski, J, Lænkholm, AV, Viale, G, Dowsett, M, Hayes, DF & Nielsen, TO 2015, 'An international study to increase concordance in Ki67 scoring', Modern Pathology, vol. 28, no. 6, pp. 778-786. https://doi.org/10.1038/modpathol.2015.38
Polley M-Y, Leung SCY, Gao D, Mastropasqua MG, Zabaglo LA, Bartlett JMS et al. An international study to increase concordance in Ki67 scoring. Modern Pathology. 2015 Jun 1;28(6):778-786. https://doi.org/10.1038/modpathol.2015.38
Polley, Mei-Yin ; Leung, Samuel C.Y. ; Gao, Dongxia ; Mastropasqua, Mauro G. ; Zabaglo, Lila A. ; Bartlett, John M.S. ; Mcshane, Lisa M. ; Enos, Rebecca A. ; Badve, Sunil S. ; Bane, Anita L. ; Borgquist, Signe ; Fineberg, Susan ; Lin, Ming Gang ; Gown, Allen M. ; Grabau, Dorthe ; Gutierrez, Carolina ; Hugh, Judith C. ; Moriya, Takuya ; Ohi, Yasuyo ; Osborne, C. Kent ; Penault-Llorca, Frédérique M. ; Piper, Tammy ; Porter, Peggy L. ; Sakatani, Takashi ; Salgado, Roberto ; Starczynski, Jane ; Lænkholm, Anne Vibeke ; Viale, Giuseppe ; Dowsett, Mitch ; Hayes, Daniel F. ; Nielsen, Torsten O. / An international study to increase concordance in Ki67 scoring. In: Modern Pathology. 2015 ; Vol. 28, No. 6. pp. 778-786.
@article{088a9e7e8627477f93efd15b0595aed7,
title = "An international study to increase concordance in Ki67 scoring",
abstract = "Although an important biomarker in breast cancer, Ki67 lacks scoring standardization, which has limited its clinical use. Our previous study found variability when laboratories used their own scoring methods on centrally stained tissue microarray slides. In this current study, 16 laboratories from eight countries calibrated to a specific Ki67 scoring method and then scored 50 centrally MIB-1 stained tissue microarray cases. Simple instructions prescribed scoring pattern and staining thresholds for determination of the percentage of stained tumor cells. To calibrate, laboratories scored 18 'training' and 'test' web-based images. Software tracked object selection and scoring. Success for the calibration was prespecified as Root Mean Square Error of scores compared with reference <0.6 and Maximum Absolute Deviation from reference <1.0 (log2-transformed data). Prespecified success criteria for tissue microarray scoring required intraclass correlation significantly >0.70 but aiming for observed intraclass correlation ≥0.90. Laboratory performance showed non-significant but promising trends of improvement through the calibration exercise (mean Root Mean Square Error decreased from 0.6 to 0.4, Maximum Absolute Deviation from 1.6 to 0.9; paired t-test: P=0.07 for Root Mean Square Error, 0.06 for Maximum Absolute Deviation). For tissue microarray scoring, the intraclass correlation estimate was 0.94 (95{\%} credible interval: 0.90-0.97), markedly and significantly >0.70, the prespecified minimum target for success. Some discrepancies persisted, including around clinically relevant cutoffs. After calibrating to a common scoring method via a web-based tool, laboratories can achieve high inter-laboratory reproducibility in Ki67 scoring on centrally stained tissue microarray slides. Although these data are potentially encouraging, suggesting that it may be possible to standardize scoring of Ki67 among pathology laboratories, clinically important discrepancies persist. Before this biomarker could be recommended for clinical use, future research will need to extend this approach to biopsies and whole sections, account for staining variability, and link to outcomes.",
author = "Mei-Yin Polley and Leung, {Samuel C.Y.} and Dongxia Gao and Mastropasqua, {Mauro G.} and Zabaglo, {Lila A.} and Bartlett, {John M.S.} and Mcshane, {Lisa M.} and Enos, {Rebecca A.} and Badve, {Sunil S.} and Bane, {Anita L.} and Signe Borgquist and Susan Fineberg and Lin, {Ming Gang} and Gown, {Allen M.} and Dorthe Grabau and Carolina Gutierrez and Hugh, {Judith C.} and Takuya Moriya and Yasuyo Ohi and Osborne, {C. Kent} and Penault-Llorca, {Fr{\'e}d{\'e}rique M.} and Tammy Piper and Porter, {Peggy L.} and Takashi Sakatani and Roberto Salgado and Jane Starczynski and L{\ae}nkholm, {Anne Vibeke} and Giuseppe Viale and Mitch Dowsett and Hayes, {Daniel F.} and Nielsen, {Torsten O.}",
year = "2015",
month = "6",
day = "1",
doi = "10.1038/modpathol.2015.38",
language = "English (US)",
volume = "28",
pages = "778--786",
journal = "Modern Pathology",
issn = "0893-3952",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - An international study to increase concordance in Ki67 scoring

AU - Polley, Mei-Yin

AU - Leung, Samuel C.Y.

AU - Gao, Dongxia

AU - Mastropasqua, Mauro G.

AU - Zabaglo, Lila A.

AU - Bartlett, John M.S.

AU - Mcshane, Lisa M.

AU - Enos, Rebecca A.

AU - Badve, Sunil S.

AU - Bane, Anita L.

AU - Borgquist, Signe

AU - Fineberg, Susan

AU - Lin, Ming Gang

AU - Gown, Allen M.

AU - Grabau, Dorthe

AU - Gutierrez, Carolina

AU - Hugh, Judith C.

AU - Moriya, Takuya

AU - Ohi, Yasuyo

AU - Osborne, C. Kent

AU - Penault-Llorca, Frédérique M.

AU - Piper, Tammy

AU - Porter, Peggy L.

AU - Sakatani, Takashi

AU - Salgado, Roberto

AU - Starczynski, Jane

AU - Lænkholm, Anne Vibeke

AU - Viale, Giuseppe

AU - Dowsett, Mitch

AU - Hayes, Daniel F.

AU - Nielsen, Torsten O.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Although an important biomarker in breast cancer, Ki67 lacks scoring standardization, which has limited its clinical use. Our previous study found variability when laboratories used their own scoring methods on centrally stained tissue microarray slides. In this current study, 16 laboratories from eight countries calibrated to a specific Ki67 scoring method and then scored 50 centrally MIB-1 stained tissue microarray cases. Simple instructions prescribed scoring pattern and staining thresholds for determination of the percentage of stained tumor cells. To calibrate, laboratories scored 18 'training' and 'test' web-based images. Software tracked object selection and scoring. Success for the calibration was prespecified as Root Mean Square Error of scores compared with reference <0.6 and Maximum Absolute Deviation from reference <1.0 (log2-transformed data). Prespecified success criteria for tissue microarray scoring required intraclass correlation significantly >0.70 but aiming for observed intraclass correlation ≥0.90. Laboratory performance showed non-significant but promising trends of improvement through the calibration exercise (mean Root Mean Square Error decreased from 0.6 to 0.4, Maximum Absolute Deviation from 1.6 to 0.9; paired t-test: P=0.07 for Root Mean Square Error, 0.06 for Maximum Absolute Deviation). For tissue microarray scoring, the intraclass correlation estimate was 0.94 (95% credible interval: 0.90-0.97), markedly and significantly >0.70, the prespecified minimum target for success. Some discrepancies persisted, including around clinically relevant cutoffs. After calibrating to a common scoring method via a web-based tool, laboratories can achieve high inter-laboratory reproducibility in Ki67 scoring on centrally stained tissue microarray slides. Although these data are potentially encouraging, suggesting that it may be possible to standardize scoring of Ki67 among pathology laboratories, clinically important discrepancies persist. Before this biomarker could be recommended for clinical use, future research will need to extend this approach to biopsies and whole sections, account for staining variability, and link to outcomes.

AB - Although an important biomarker in breast cancer, Ki67 lacks scoring standardization, which has limited its clinical use. Our previous study found variability when laboratories used their own scoring methods on centrally stained tissue microarray slides. In this current study, 16 laboratories from eight countries calibrated to a specific Ki67 scoring method and then scored 50 centrally MIB-1 stained tissue microarray cases. Simple instructions prescribed scoring pattern and staining thresholds for determination of the percentage of stained tumor cells. To calibrate, laboratories scored 18 'training' and 'test' web-based images. Software tracked object selection and scoring. Success for the calibration was prespecified as Root Mean Square Error of scores compared with reference <0.6 and Maximum Absolute Deviation from reference <1.0 (log2-transformed data). Prespecified success criteria for tissue microarray scoring required intraclass correlation significantly >0.70 but aiming for observed intraclass correlation ≥0.90. Laboratory performance showed non-significant but promising trends of improvement through the calibration exercise (mean Root Mean Square Error decreased from 0.6 to 0.4, Maximum Absolute Deviation from 1.6 to 0.9; paired t-test: P=0.07 for Root Mean Square Error, 0.06 for Maximum Absolute Deviation). For tissue microarray scoring, the intraclass correlation estimate was 0.94 (95% credible interval: 0.90-0.97), markedly and significantly >0.70, the prespecified minimum target for success. Some discrepancies persisted, including around clinically relevant cutoffs. After calibrating to a common scoring method via a web-based tool, laboratories can achieve high inter-laboratory reproducibility in Ki67 scoring on centrally stained tissue microarray slides. Although these data are potentially encouraging, suggesting that it may be possible to standardize scoring of Ki67 among pathology laboratories, clinically important discrepancies persist. Before this biomarker could be recommended for clinical use, future research will need to extend this approach to biopsies and whole sections, account for staining variability, and link to outcomes.

UR - http://www.scopus.com/inward/record.url?scp=84930177652&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930177652&partnerID=8YFLogxK

U2 - 10.1038/modpathol.2015.38

DO - 10.1038/modpathol.2015.38

M3 - Article

C2 - 25698062

AN - SCOPUS:84930177652

VL - 28

SP - 778

EP - 786

JO - Modern Pathology

JF - Modern Pathology

SN - 0893-3952

IS - 6

ER -