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

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.

SUBMITTER: Acs B

PROVIDER: S-EPMC9514990 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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

Acs Balazs B Leung Samuel C Y SCY Kidwell Kelley M KM Arun Indu I Augulis Renaldas R Badve Sunil S SS Bai Yalai Y Bane Anita L AL Bartlett John M S JMS Bayani Jane J Bigras Gilbert G Blank Annika A Buikema Henk H Chang Martin C MC Dietz Robin L RL Dodson Andrew A Fineberg Susan S Focke Cornelia M CM Gao Dongxia D Gown Allen M AM Gutierrez Carolina C Hartman Johan J Kos Zuzana Z Lænkholm Anne-Vibeke AV Laurinavicius Arvydas A Levenson Richard M RM Mahboubi-Ardakani Rustin R Mastropasqua Mauro G MG Nofech-Mozes Sharon S Osborne C Kent CK Penault-Llorca Frédérique M FM Piper Tammy T Quintayo Mary Anne MA Rau Tilman T TT Reinhard Stefan S Robertson Stephanie S Salgado Roberto R Sugie Tomoharu T van der Vegt Bert B Viale Giuseppe G Zabaglo Lila A LA Hayes Daniel F DF Dowsett Mitch M Nielsen Torsten O TO Rimm David L DL

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 20220621 10

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 r ...[more]

PMID: 35729220

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Project description:Background and objectivePatients diagnosed with grade group (GG) 1 prostate cancer (PCa) following treatment for benign disease ("incidental" PCa) are typically managed with active surveillance (AS). It is not known how their outcomes compare with those observed in patients diagnosed with GG1 on biopsy. We aimed at determining whether long-term oncologic outcomes of AS for patients with GG1 PCa differ according to the type of diagnosis: incidental versus biopsy detected.MethodsA retrospective, multi-institutional analysis of PCa patients with GG1 on AS at eight institutions was conducted. Competing risk analyses estimated the incidence of metastases, PCa mortality, and conversion to treatment. As a secondary analysis, we estimated the risk of GG ≥2 on the first follow-up biopsy according to the type of initial diagnosis.Key findings and limitationsA total of 213 versus 1900 patients with incidental versus biopsy-diagnosed GG1 were identified. Patients with incidental cancers were followed with repeated biopsies and multiparametric magnetic resonance imaging less frequently than those diagnosed on biopsy. The 10-yr incidence of treatment was 22% for incidental cancers versus 53% for biopsy (subdistribution hazard ratio [sHR] 0.34, 95% confidence interval [CI] 0.26-0.46, p < 0.001). Distant metastases developed in one patient with incidental cancer versus 17 diagnosed on biopsy and were diagnosed with molecular imaging in 13 (72%) patients. The 10-yr incidence of metastases was 0.8% for patients with incidental PCa and 2% for those diagnosed on biopsy (sHR 0.35, 95% CI 0.05-2.54, p = 0.3). The risk of GG ≥2 on the first follow-up biopsy was low if the initial diagnosis was incidental (7% vs 22%, p < 0.001).Conclusions and clinical implicationsPatients with GG1 incidental PCa should be evaluated further to exclude aggressive disease, preferably with a biopsy. If no cancer is found on biopsy, then they should receive the same follow-up of a patient with a negative biopsy. Further research should confirm whether imaging and biopsies can be avoided if postoperative prostate-specific antigen is low (<1-2 ng/ml).Patient summaryWe compared the outcomes of patients with low-grade prostate cancer on active surveillance according to the type of their initial diagnosis. Patients who have low-grade cancer diagnosed on a procedure to relieve urinary symptoms (incidental prostate cancer) are followed less intensively and undergo curative-intended treatment less frequently. We also found that patients with incidental prostate cancer are more likely to have no cancer on their first follow-up biopsy than patients who have low-grade cancer initially diagnosed on a biopsy. These patients have a more favorable prognosis than their biopsy-detected counterparts and should be managed the same way as patients with negative biopsies if they undergo a subsequent biopsy that shows no cancer.

Dataset Information

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

Publications

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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