Automated Ki-67 labeling index assessment in prostate cancer using artificial intelligence and multiplex fluorescence immunohistochemistry
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Automated Ki-67 labeling index assessment in prostate cancer using artificial intelligence and multiplex fluorescence immunohistochemistry. / Blessin, Niclas C; Yang, Cheng; Mandelkow, Tim; Raedler, Jonas B; Li, Wenchao; Bady, Elena; Simon, Ronald; Vettorazzi, Eik; Lennartz, Maximilian; Bernreuther, Christian; Fraune, Christoph; Jacobsen, Frank; Krech, Till; Marx, Andreas; Lebok, Patrick; Minner, Sarah; Burandt, Eike; Clauditz, Till S; Wilczak, Waldemar; Sauter, Guido; Heinzer, Hans; Haese, Alexander; Schlomm, Thorsten; Graefen, Markus; Steurer, Stefan.
In: J PATHOL, Vol. 260, No. 1, 05.2023, p. 5-16.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Automated Ki-67 labeling index assessment in prostate cancer using artificial intelligence and multiplex fluorescence immunohistochemistry
AU - Blessin, Niclas C
AU - Yang, Cheng
AU - Mandelkow, Tim
AU - Raedler, Jonas B
AU - Li, Wenchao
AU - Bady, Elena
AU - Simon, Ronald
AU - Vettorazzi, Eik
AU - Lennartz, Maximilian
AU - Bernreuther, Christian
AU - Fraune, Christoph
AU - Jacobsen, Frank
AU - Krech, Till
AU - Marx, Andreas
AU - Lebok, Patrick
AU - Minner, Sarah
AU - Burandt, Eike
AU - Clauditz, Till S
AU - Wilczak, Waldemar
AU - Sauter, Guido
AU - Heinzer, Hans
AU - Haese, Alexander
AU - Schlomm, Thorsten
AU - Graefen, Markus
AU - Steurer, Stefan
N1 - This article is protected by copyright. All rights reserved.
PY - 2023/5
Y1 - 2023/5
N2 - The Ki-67 labeling index (Ki-67 LI) is a strong prognostic marker in prostate cancer, although its analysis requires cumbersome manual quantification of Ki-67 immunostaining in 200-500 tumor cells. To enable automated Ki-67 LI assessment in routine clinical practice, a framework for automated Ki-67 LI quantification, which comprises three different artificial intelligence analysis steps and an algorithm for cell-distance analysis of multiplex fluorescence immunohistochemistry (mfIHC) staining, was developed and validated in a cohort of 12,475 prostate cancers. The prognostic impact of the Ki-67 LI was tested on a tissue microarray (TMA) containing one 0.6 mm sample per patient. A 'heterogeneity TMA' containing three to six samples from different tumor areas in each patient was used to model Ki-67 analysis of multiple different biopsies, and 30 prostate biopsies were analyzed to compare a 'classical' bright field-based Ki-67 analysis with the mfIHC-based framework. The Ki-67 LI provided strong and independent prognostic information in 11,845 analyzed prostate cancers (p < 0.001 each), and excellent agreement was found between the framework for automated Ki-67 LI assessment and the manual quantification in prostate biopsies from routine clinical practice (intraclass correlation coefficient: 0.94 [95% confidence interval: 0.87-0.97]). The analysis of the heterogeneity TMA revealed that the Ki-67 LI of the sample with the highest Gleason score (area under the curve [AUC]: 0.68) was as prognostic as the mean Ki-67 LI of all six foci (AUC: 0.71 [p = 0.24]). The combined analysis of the Ki-67 LI and Gleason score obtained on identical tissue spots showed that the Ki-67 LI added significant additional prognostic information in case of classical International Society of Urological Pathology grades (AUC: 0.82 [p = 0.002]) and quantitative Gleason score (AUC: 0.83 [p = 0.018]). The Ki-67 LI is a powerful prognostic parameter in prostate cancer that is now applicable in routine clinical practice. In the case of multiple cancer-positive biopsies, the sole automated analysis of the worst biopsy was sufficient. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
AB - The Ki-67 labeling index (Ki-67 LI) is a strong prognostic marker in prostate cancer, although its analysis requires cumbersome manual quantification of Ki-67 immunostaining in 200-500 tumor cells. To enable automated Ki-67 LI assessment in routine clinical practice, a framework for automated Ki-67 LI quantification, which comprises three different artificial intelligence analysis steps and an algorithm for cell-distance analysis of multiplex fluorescence immunohistochemistry (mfIHC) staining, was developed and validated in a cohort of 12,475 prostate cancers. The prognostic impact of the Ki-67 LI was tested on a tissue microarray (TMA) containing one 0.6 mm sample per patient. A 'heterogeneity TMA' containing three to six samples from different tumor areas in each patient was used to model Ki-67 analysis of multiple different biopsies, and 30 prostate biopsies were analyzed to compare a 'classical' bright field-based Ki-67 analysis with the mfIHC-based framework. The Ki-67 LI provided strong and independent prognostic information in 11,845 analyzed prostate cancers (p < 0.001 each), and excellent agreement was found between the framework for automated Ki-67 LI assessment and the manual quantification in prostate biopsies from routine clinical practice (intraclass correlation coefficient: 0.94 [95% confidence interval: 0.87-0.97]). The analysis of the heterogeneity TMA revealed that the Ki-67 LI of the sample with the highest Gleason score (area under the curve [AUC]: 0.68) was as prognostic as the mean Ki-67 LI of all six foci (AUC: 0.71 [p = 0.24]). The combined analysis of the Ki-67 LI and Gleason score obtained on identical tissue spots showed that the Ki-67 LI added significant additional prognostic information in case of classical International Society of Urological Pathology grades (AUC: 0.82 [p = 0.002]) and quantitative Gleason score (AUC: 0.83 [p = 0.018]). The Ki-67 LI is a powerful prognostic parameter in prostate cancer that is now applicable in routine clinical practice. In the case of multiple cancer-positive biopsies, the sole automated analysis of the worst biopsy was sufficient. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
U2 - 10.1002/path.6057
DO - 10.1002/path.6057
M3 - SCORING: Journal article
C2 - 36656126
VL - 260
SP - 5
EP - 16
JO - J PATHOL
JF - J PATHOL
SN - 0022-3417
IS - 1
ER -