Independent Clinical Validation of the Automated Ki67 Scoring Guideline from the International Ki67 in Breast Cancer Working Group
Ki67 is an important biomarker with prognostic and potential predictive value in breast cancer. However, the lack of standardization hinders its clinical applicability. In this study, we aimed to investigate the reproducibility among pathologists following the guidelines of the International Ki67 in...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/11/1612 |
| _version_ | 1797511083782569984 |
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| author | Ceren Boyaci Wenwen Sun Stephanie Robertson Balazs Acs Johan Hartman |
| author_facet | Ceren Boyaci Wenwen Sun Stephanie Robertson Balazs Acs Johan Hartman |
| author_sort | Ceren Boyaci |
| collection | DOAJ |
| description | Ki67 is an important biomarker with prognostic and potential predictive value in breast cancer. However, the lack of standardization hinders its clinical applicability. In this study, we aimed to investigate the reproducibility among pathologists following the guidelines of the International Ki67 in Breast Cancer Working Group (IKWG) for Ki67 scoring and to evaluate the prognostic potential of this platform in an independent cohort. Four algorithms were independently built by four pathologists based on our study cohort using an open-source digital image analysis (DIA) platform (QuPath) following the detailed guideline of the IKWG. The algorithms were applied on an ER+ breast cancer study cohort of 157 patients with 15 years of follow-up. The reference Ki67 score was obtained by a DIA algorithm trained on a subset of the study cohort. Intraclass correlation coefficient (ICC) was used to measure reproducibility. High interobserver reliability was reached with an ICC of 0.938 (CI: 0.920–0.952) among the algorithms and the reference standard. Comparing each machine-read score against relapse-free survival, the hazard ratios were similar (2.593–4.165) and showed independent prognostic potential (<i>p</i> ≤ 0.018, for all comparisons). In conclusion, we demonstrate high reproducibility and independent prognostic potential using the IKWG DIA instructions to score Ki67 in breast cancer. A prospective study is needed to assess the clinical utility of the IKWG DIA Ki67 instructions. |
| first_indexed | 2024-03-10T05:40:24Z |
| format | Article |
| id | doaj.art-8c9be16dc039410b9146f7c5b994c8a5 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T05:40:24Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-8c9be16dc039410b9146f7c5b994c8a52023-11-22T22:33:44ZengMDPI AGBiomolecules2218-273X2021-10-011111161210.3390/biom11111612Independent Clinical Validation of the Automated Ki67 Scoring Guideline from the International Ki67 in Breast Cancer Working GroupCeren Boyaci0Wenwen Sun1Stephanie Robertson2Balazs Acs3Johan Hartman4Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, 11883 Stockholm, SwedenDepartment of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, 11883 Stockholm, SwedenDepartment of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, 11883 Stockholm, SwedenDepartment of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, 11883 Stockholm, SwedenDepartment of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, 11883 Stockholm, SwedenKi67 is an important biomarker with prognostic and potential predictive value in breast cancer. However, the lack of standardization hinders its clinical applicability. In this study, we aimed to investigate the reproducibility among pathologists following the guidelines of the International Ki67 in Breast Cancer Working Group (IKWG) for Ki67 scoring and to evaluate the prognostic potential of this platform in an independent cohort. Four algorithms were independently built by four pathologists based on our study cohort using an open-source digital image analysis (DIA) platform (QuPath) following the detailed guideline of the IKWG. The algorithms were applied on an ER+ breast cancer study cohort of 157 patients with 15 years of follow-up. The reference Ki67 score was obtained by a DIA algorithm trained on a subset of the study cohort. Intraclass correlation coefficient (ICC) was used to measure reproducibility. High interobserver reliability was reached with an ICC of 0.938 (CI: 0.920–0.952) among the algorithms and the reference standard. Comparing each machine-read score against relapse-free survival, the hazard ratios were similar (2.593–4.165) and showed independent prognostic potential (<i>p</i> ≤ 0.018, for all comparisons). In conclusion, we demonstrate high reproducibility and independent prognostic potential using the IKWG DIA instructions to score Ki67 in breast cancer. A prospective study is needed to assess the clinical utility of the IKWG DIA Ki67 instructions.https://www.mdpi.com/2218-273X/11/11/1612Ki67breast cancerQuPathdigital image analysisvalidationreproducibility |
| spellingShingle | Ceren Boyaci Wenwen Sun Stephanie Robertson Balazs Acs Johan Hartman Independent Clinical Validation of the Automated Ki67 Scoring Guideline from the International Ki67 in Breast Cancer Working Group Biomolecules Ki67 breast cancer QuPath digital image analysis validation reproducibility |
| title | Independent Clinical Validation of the Automated Ki67 Scoring Guideline from the International Ki67 in Breast Cancer Working Group |
| title_full | Independent Clinical Validation of the Automated Ki67 Scoring Guideline from the International Ki67 in Breast Cancer Working Group |
| title_fullStr | Independent Clinical Validation of the Automated Ki67 Scoring Guideline from the International Ki67 in Breast Cancer Working Group |
| title_full_unstemmed | Independent Clinical Validation of the Automated Ki67 Scoring Guideline from the International Ki67 in Breast Cancer Working Group |
| title_short | Independent Clinical Validation of the Automated Ki67 Scoring Guideline from the International Ki67 in Breast Cancer Working Group |
| title_sort | independent clinical validation of the automated ki67 scoring guideline from the international ki67 in breast cancer working group |
| topic | Ki67 breast cancer QuPath digital image analysis validation reproducibility |
| url | https://www.mdpi.com/2218-273X/11/11/1612 |
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