Systematically higher Ki67 scores on core biopsy samples compared to corresponding resection specimen in breast cancer: a multi-operator and multi-institutional study
Balázs Ács, Samuel Leung, Kelley M. Kidwell, Indu Arun, Renaldas Augulis, Sunil Badve, Yalai Bai, Anita Bane, John M.S. Bartlett, Jane Bayani, Gilbert Bigras, Annika Blank, Henk J. Buikema, Martin C. Chang, R Dietz, Andrew Dodson, Susan Fineberg, Cornelia M. Focke, Dongxia Gao, Allen M. Gown, Carolina Gutiérrez, Johan Hartman, Zuzana Kos, Anne‐Vibeke Lænkholm, Arvydas Laurinavičius, Richard M. Levenson, R. Mahboubi-Ardakani, Mauro G. Mastropasqua, Sharon Nofech‐Mozes, C. Kent Osborne, Frédérique Penault‐Llorca, Tammy Piper, Mary Anne Quintayo, Tilman T. Rau, Stefan Reinhard, Stephanie Robertson, Roberto Salgado, Tomoharu Sugie, Bert van der Vegt, Giuseppe Viale, Lila Zabaglo, Daniel F. Hayes, Mitch Dowsett, Torsten O. Nielsen, David L. Rimm, Mitch Dowsett, Daniel F. Hayes, Lisa M. McShane, Kelley M. Kidwell, Torsten O. Nielsen, Samuel Leung, Balázs Ács, Indu Arun, Renaldas Augulis, Sunil Badve, Yalai Bai, Anita Bane, John M.S. Bartlett, Jane Bayani, Gilbert Bigras, Annika Blank, Signe Borgquist, Henk J. Buikema, Angela Chan, Martin C. Chang, Carsten Denkert, R Dietz, Andrew Dodson, Anna Ehinger, Matthew J. Ellis, Susan Fineberg, Margaret Flowers, Cornelia M. Focke, Chad Galderisi, Dongxia Gao, Abhi Gholap, Allen M. Gown, Carolina Gutiérrez, Douglas J. Hartman, Johan Hartman, Judith Hugh, Anagha P. Jadhav, Elizabeth Kornaga, Zuzana Kos, Hans Kreipe, Anne‐Vibeke Lænkholm, Arvydas Laurinavičius, Richard M. Levenson, Mauro Mastropasqua, Takuya Moriya, Sharon Nofech‐Mozes, C. Kent Osborne, Hongchao Pan, Liron Pantanowitz, Ernesta Paola Neri, Frédérique Penault‐Llorca, Mei‐Yin C. Polley, Tammy Piper, Mary Anne Quintayo, Tilman T. Rau
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.