Systematically higher Ki67 scores on core biopsy samples compared to corresponding resection specimen in breast cancer: a multi-operator and multi-institutional study

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  • Balazs Acs
  • on behalf of the International Ki67 in Breast Cancer Working Group of the Breast International Group and North American Breast Cancer Group (BIG-NABCG)

Ki67 has potential clinical importance in breast cancer but has yet to see broad acceptance due to inter-laboratory variability. Here we tested an open source and calibrated automated digital image analysis (DIA) platform to: (i) investigate the comparability of Ki67 measurement across corresponding core biopsy and resection specimen cases, and (ii) assess section to section differences in Ki67 scoring. Two sets of 60 previously stained slides containing 30 core-cut biopsy and 30 corresponding resection specimens from 30 estrogen receptor-positive breast cancer patients were sent to 17 participating labs for automated assessment of average Ki67 expression. The blocks were centrally cut and immunohistochemically (IHC) stained for Ki67 (MIB-1 antibody). The QuPath platform was used to evaluate tumoral Ki67 expression. Calibration of the DIA method was performed as in published studies. A guideline for building an automated Ki67 scoring algorithm was sent to participating labs. Very high correlation and no systematic error (p = 0.08) was found between consecutive Ki67 IHC sections. Ki67 scores were higher for core biopsy slides compared to paired whole sections from resections (p ≤ 0.001; median difference: 5.31%). The systematic discrepancy between core biopsy and corresponding whole sections was likely due to pre-analytical factors (tissue handling, fixation). Therefore, Ki67 IHC should be tested on core biopsy samples to best reflect the biological status of the tumor.

OriginalsprogEngelsk
TidsskriftModern Pathology
Vol/bind35
Udgave nummer10
Sider (fra-til)1362-1369
Antal sider8
ISSN0893-3952
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
We are grateful to the Breast International Group and North American Breast Cancer Group (BIG-NABCG) collaboration, including the leadership of Nancy Davidson, Thomas Buchholz, Martine Piccart, and Larry Norton.

Funding Information:
BA is supported by The Swedish Society for Medical Research (Svenska Sällskapet för Medicinsk Forskning) Postdoctoral grant, Swedish Breast Cancer Association (Bröstcancerförbundet) Research grant 2021, The Fulbright Program and The Rosztoczy Foundation Scholarship Program. MD, DFH, RS (BCRF grant N° 17–194), (many others) and DLR are supported by the Breast Cancer Research Foundation. This work was supported by a generous grant from the Breast Cancer Research Foundation (DFH). Additional funding for the UK laboratories was received from Breakthrough Breast Cancer and the National Institute for Health Research Biomedical Research Centre at the Royal Marsden Hospital. Funding for the Ontario Institute for Cancer Research is provided by the Government of Ontario. JH is the Lilian McCullough Chair in Breast Cancer Surgery Research and the CBCF Prairies/NWT Chapter. Open access funding provided by Karolinska Institute.

Funding Information:
In the last 12 months, DLR has served as a consultant for advisor to Astra Zeneca, Agendia, Amgen, Cell Signaling Technology, Cepheid, Danaher, Konica-Minolta, Merck, PAIGE.AI, Regeneron, and Sanofi. TON reports a proprietary interest in PAM50/Prosigna and consultant work with Veracyte. JH was former member of the advisory board at Visiopharm A/S. JH has obtained speaker’s honoraria or advisory board remunerations from Roche, Novartis, AstraZeneca, Eli Lilly, Pfizer and MSD. JH is co-founder and shareholder of Stratipath AB. JH has received institutional research grants from Cepheid and Novartis. DFH reports no research or personal financial support related to this study. DFH does report research support unrelated to this study provided to his institution during conduct from Menarini/Silicon BioSystems, Astra Zeneca, Eli Lilly Company, Merrimack Pharmaceuticals, Inc. (Parexel Intl Corp), Veridex and Janssen Diagnostics (Johnson & Johnson), Pfizer, and Puma Biotechnology, Inc. (subcontract Wash Univ St. Louis to Univ Mich). DFH also reports that his institution holds a patent regarding circulating tumor cell characterization for which DFH is the named investigator that was licensed to Menarini Silicon Biosystems and from which both received annual royalties, ending in January 2021. DFH reports personal income related to consulting or advisory board activities from BioVeca, Cellworks, Cepheid, EPIC Sciences, Freenome, Guardant, L-Nutra, Oncocyte, Macrogenics, Predictus BioSciences, Salutogenic Innovations, Turnstone Biologics, and Tempus. DFH reports personally held stock options from InBiomotion. BvdV reports speaker’s honoraria or consultation/advisory board remunerations provided to his institution from Visiopharm, Philips, Merck/MSD and Diaceutics. GV reports receipt of grants/research supports from Roche/Genentech, Ventana Medical Systems, Dako/Agilent Technologies, and receipt of honoraria or consultation fees from Ventana, Dako/Agilent, Roche, MSD Oncology, AstraZeneca, Daiichi Sankyo, Pfizer, Eli Lilly. ZK has served in a paid advisory role to Eli Lilly. Unrelated to this study, SR is currently employed by Stratipath AB. RS reports non-financial support from Merck and Bristol Myers Squibb; research support from Merck, Puma Biotechnology, and Roche; and advisory board fees for Bristol Myers Squibb; and personal fees from Roche for an advisory board related to a trial-research project. RS has no COI related to this project. SF served as expert pathology consultant for Axdev Global Corp inc and as an expert advisory panel for Genomic Health in 2017. RML is co-founder and shareholder of MUSE Microscopy, Inc. and Histolix, Inc. RML served as consultant for Cell IDx, Inc., BriteSeed, Inc., ImmunoPhotonics, Inc., Pathology Watch, Inc. and Verily, Inc. FPL reports board meetings and conference support from Astrazeneca, Lilly, Novartis, Pfizer and Roche. JB served as consultant for Insight Genetics, Inc., BioNTech AG, Biotheranostics, Inc., Pfizer, Rna Diagnostics Inc., oncoXchange/MedcomXchange Communications Inc, Herbert Smith French Solicitors, OncoCyte Corporation. JB served as member of the scientific advisory board for MedcomXchange Communications Inc. JB reports honoraria from NanoString Technologies, Inc., Oncology Education, Biotheranostics, Inc., MedcomXchange Communications Inc. JB reports travel and accommodation expenses support from Biotheranostics, Inc., NanoString Technologies, Inc., Breast Cancer Society of Canada. JB received research funding from Thermo Fisher Scientific, Genoptix, Agendia, NanoString Technologies, Inc., Stratifyer GmbH, Biotheranostics, Inc. The remaining authors declare no competing interests.

Publisher Copyright:
© 2022, The Author(s).

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