TY - JOUR
T1 - An international study to increase concordance in Ki67 scoring
AU - Polley, Mei Yin C
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 0.70 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 0.70 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.
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U2 - 10.1038/modpathol.2015.38
DO - 10.1038/modpathol.2015.38
M3 - Article
C2 - 25698062
AN - SCOPUS:84930177652
SN - 0893-3952
VL - 28
SP - 778
EP - 786
JO - Modern Pathology
JF - Modern Pathology
IS - 6
ER -