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

• Type of Material: Article
• Authors: Balazs Acs, Yale University; Sameul CY Leung, University of British Columbia; Kelly M Kidwell, University of Michigan; Indu Arun, Tata Medical Center; Renaldas Augulis, Vilnius University; Sunil Badve, Emory University; Yalai Bai, Yale University; Anita L Bane, McMaster University; John MS Bartlett, Ontario Institute for Cancer Research; Jane Bayani, Ontario Institute for Cancer Research; Gilbert Bigras, University of Alberta; Annika Blank, University of Bern; Henk Buikema, University of Groningen; Martin C Chang, University of Vermont; Robin L Dietz, Olive View-UCLA Medical Center; Andrew Dodson, UK NEQAS for Immunocytochemistry and In-Situ Hybridisation; Susan Fineberg, Montefiore Medical Center; Cornelia M Focke, Dietrich-Bonhoeffer Medical Center; Dongxia Gao, University of British Columbia; Allen M Gown, PhenoPath Laboratories; Carolina Gutierrez, Baylor College of Medicine; Johan Hartman, Karolinska Institutet; Zuzana Kos, University of British Columbia; Anne-Vibeke Lænkholm, Zealand University Hospital; Arvydas Laurinavicius, Vilnius University; Richard M Levenson, University of California Davis; Rustin Mahboubi-Ardakani, University of California Davis; Mauro G Mastropasqua, European Institute of Oncology; Sharon Nofech-Mozes, University of Toronto; Kent C Osborne, Baylor College of Medicine; Frédérique M Penault-Llorca, Université Clermont Auvergne; Tammy Piper, Western General Hospital; Mary Anne Quintayo, Ontario Institute for Cancer Research; Tilman T Rau, University of Bern; Stefan Reinhard, University of Bern; Stephan Robertson, Karolinska Institutet; Roberto Salgado, GZA-ZNA, Antwerp; Tomoharu Sugie, Kansai Medical University; Bert van der Vegt, University of Groningen; Giuseppe Viale, European Institute of Oncology; Lila A Zabaglo, Inst Canc Res; Daniel F Hayes, University of Michigan; Mitch Dowsett, The Institute of Cancer Research, London; Torsten O Nielsen, University of British Columbia; David L Rimm, Yale University
• Language: English
• Date: 2022-06-21
• Publisher: SPRINGERNATURE
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41379-022-01104-9
• Title of Journal or Parent Work: MODERN PATHOLOGY
• Volume: 35
• Issue: 10
• Start Page: 1362
• End Page: 1369
• Grant/Funding Information: Open access funding provided by Karolinska Institute.; 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.; 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).
• Keywords: MULTICENTER; Science & Technology; Pathology; BIOMARKER ASSESSMENT; REPRODUCIBILITY; NEEDLE BIOPSIES; INTERNATIONAL KI67; Life Sciences & Biomedicine; RELIABILITY; DIGITAL-IMAGE-ANALYSIS; IMMUNOHISTOCHEMISTRY; PROLIFERATION; KI-67 LABELING INDEX
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Oncology; Health Sciences, Pathology

Abstract

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.