Analytical validation of a standardised scoring protocol for Ki67 immunohistochemistry on breast cancer excision whole sections: an international multicentre collaboration.
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ICR Authors
Authors
Leung, SCY
Nielsen, TO
Zabaglo, LA
Arun, I
Badve, SS
Bane, AL
Bartlett, JMS
Borgquist, S
Chang, MC
Dodson, A
Ehinger, A
Fineberg, S
Focke, CM
Gao, D
Gown, AM
Gutierrez, C
Hugh, JC
Kos, Z
Laenkholm, A-V
Mastropasqua, MG
Moriya, T
Nofech-Mozes, S
Osborne, CK
Penault-Llorca, FM
Piper, T
Sakatani, T
Salgado, R
Starczynski, J
Sugie, T
van der Vegt, B
Viale, G
Hayes, DF
McShane, LM
Dowsett, M
International Ki67 in Breast Cancer Working Group of the Breast International Group and North American Breast Cancer Group (BIG-NABCG),
Nielsen, TO
Zabaglo, LA
Arun, I
Badve, SS
Bane, AL
Bartlett, JMS
Borgquist, S
Chang, MC
Dodson, A
Ehinger, A
Fineberg, S
Focke, CM
Gao, D
Gown, AM
Gutierrez, C
Hugh, JC
Kos, Z
Laenkholm, A-V
Mastropasqua, MG
Moriya, T
Nofech-Mozes, S
Osborne, CK
Penault-Llorca, FM
Piper, T
Sakatani, T
Salgado, R
Starczynski, J
Sugie, T
van der Vegt, B
Viale, G
Hayes, DF
McShane, LM
Dowsett, M
International Ki67 in Breast Cancer Working Group of the Breast International Group and North American Breast Cancer Group (BIG-NABCG),
Document Type
Journal Article
Date
2016-02-10
Date Accepted
2019-04-19
Abstract
AIMS: The nuclear proliferation marker Ki67 assayed by immunohistochemistry has multiple potential uses in breast cancer, but an unacceptable level of interlaboratory variability has hampered its clinical utility. The International Ki67 in Breast Cancer Working Group has undertaken a systematic programme to determine whether Ki67 measurement can be analytically validated and standardised among laboratories. This study addresses whether acceptable scoring reproducibility can be achieved on excision whole sections. METHODS AND RESULTS: Adjacent sections from 30 primary ER+ breast cancers were centrally stained for Ki67 and sections were circulated among 23 pathologists in 12 countries. All pathologists scored Ki67 by two methods: (i) global: four fields of 100 tumour cells each were selected to reflect observed heterogeneity in nuclear staining; (ii) hot-spot: the field with highest apparent Ki67 index was selected and up to 500 cells scored. The intraclass correlation coefficient (ICC) for the global method [confidence interval (CI) = 0.87; 95% CI = 0.799-0.93] marginally met the prespecified success criterion (lower 95% CI ≥ 0.8), while the ICC for the hot-spot method (0.83; 95% CI = 0.74-0.90) did not. Visually, interobserver concordance in location of selected hot-spots varies between cases. The median times for scoring were 9 and 6 min for global and hot-spot methods, respectively. CONCLUSIONS: The global scoring method demonstrates adequate reproducibility to warrant next steps towards evaluation for technical and clinical validity in appropriate cohorts of cases. The time taken for scoring by either method is practical using counting software we are making publicly available. Establishment of external quality assessment schemes is likely to improve the reproducibility between laboratories further.
Citation
Histopathology, 2019, 75 (2), pp. 225 - 235
Source Title
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
0309-0167
eISSN
1365-2559
Collections
Research Team
Endocrinology