Digital quantification of KI-67 in breast cancer

Sanchez, Malka Huici; Soler-Monsó, Teresa; Petit, Audrey; Azcarate, Juan; Lasheras, Alba; Artal, Carmen; Gil, Miguel Ángel Cobos; Falo, Catalina; Jesús, María; Matías‐Guiu, Xavier

doi:10.1007/s00428-018-2481-3

Cited by 18 publications

(23 citation statements)

References 19 publications

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“…There are several DIA platforms offering a solution for scoring Ki67. Although studies have shown both high correlations between machine-read and manual scores and good interplatform agreement [ 25 , 26 ], none of these platforms have reached clinical utility yet. In our study, we confirmed the prognostic potential of the automated Ki67 scoring guideline proposed by the IKWG.…”

Section: Discussionmentioning

confidence: 99%

Independent Clinical Validation of the Automated Ki67 Scoring Guideline from the International Ki67 in Breast Cancer Working Group

et al. 2021

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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 (p ≤ 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.

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Section: Discussionmentioning

confidence: 99%

Independent Clinical Validation of the Automated Ki67 Scoring Guideline from the International Ki67 in Breast Cancer Working Group

et al. 2021

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“…For this reason, the International Ki67 in Breast Cancer Working Group recently agreed that Ki67 IHC could be used in the decision-making treatment only if the results are below 5% and above 30% 16 , 17 . In an attempt to reduce the effect of all these variables, digital counting methods for this and other IHC biomarkers have been developed, with most presenting good correlation coefficients 18 , 19 . However, it is generally considered preferable to analyze gene expression signatures for prognostic purposes in luminal cancers when affordable and adequate reproducibility is not guaranteed 3 .…”

Section: Introductionmentioning

confidence: 99%

Conventional and digital Ki67 evaluation and their correlation with molecular prognosis and morphological parameters in luminal breast cancer

Pons

Hernández-León

Altaleb

et al. 2022

Sci Rep

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Digital counting methods were developed to decrease the high intra- and inter-observer variability of immunohistochemical markers such as Ki67, with most presenting a good correlation coefficient (CC). Since Ki67 is one of the major contributors to Oncotype DX, it is conceivable that Ki67 expression and the recurrence score (RS) obtained by the multigene panel are positively correlated. We decided first to test to what extent conventional and digital Ki67 quantification methods correlate in daily practice and, second, to determine which of these methods correlates better with the prognostic capacity of the Oncotype DX test. Both Ki67 evaluations were performed in 89 core biopsies with a diagnosis of estrogen receptor (ER) positive HER2-negative breast cancer (BC). Cases were, thus, classified twice for surrogate subtype: first by conventional analysis and then by digital evaluation. The Oncotype RS was obtained in 55 cases that were subsequently correlated to Ki67 evaluation by both methods. Conventional and digital Ki67 evaluation showed good concordance and correlation (CC = 0.81 (95% CI 0.73–0.89)). The correlation of Oncotype DX risk groups and surrogate derived subtypes was slightly higher for the digital technique (rs = 0.46, p < 0.01) compared to the conventional method (rs = 0.39, p < 0.01), even though both were statistically significant. In conclusion, we show that digital evaluation could be an alternative to conventional counting, and also has advantages for predicting the risk established by the Oncotype DX test in ER-positive BC. This study also supports the importance of an accurate Ki67 analysis which can influence the decision to submit ER-positive HER2-negative BC to prognostic molecular platforms.

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“…(C) Weight of the PDX tumor treated with vehicle, gemcitabine and 36l . (D) Quantification of Ki-67 positive cells 38 . (E) Representative images of H&E staining and IHC staining for Ki-67 of tumor tissues treated by vehicle, gemcitabine and 36l .…”

Section: Resultsmentioning

confidence: 99%

Discovery of novel KRAS‒PDEδ inhibitors with potent activity in patient-derived human pancreatic tumor xenograft models

Chen

Zhang

Wang

et al. 2022

Acta Pharmaceutica Sinica B

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KRAS‒PDE δ interaction is revealed as a promising target for suppressing the function of mutant KRAS. The bottleneck in clinical development of PDE δ inhibitors is the poor antitumor activity of known chemotypes. Here, we identified novel spiro-cyclic PDE δ inhibitors with potent antitumor activity both in vitro and in vivo . In particular, compound 36l ( K D = 127 ± 16 nmol/L) effectively bound to PDE δ and interfered with KRAS–PDE δ interaction. It influenced the distribution of KRAS in Mia PaCa-2 cells, downregulated the phosphorylation of t-ERK and t-AKT and promoted apoptosis of the cells. The novel inhibitor 36l exhibited significant in vivo antitumor potency in pancreatic cancer patient-derived xenograft (PDX) models. It represents a promising lead compound for investigating the druggability of KRAS‒PDE δ interaction.

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Digital quantification of KI-67 in breast cancer

Cited by 18 publications

References 19 publications

Independent Clinical Validation of the Automated Ki67 Scoring Guideline from the International Ki67 in Breast Cancer Working Group

Independent Clinical Validation of the Automated Ki67 Scoring Guideline from the International Ki67 in Breast Cancer Working Group

Conventional and digital Ki67 evaluation and their correlation with molecular prognosis and morphological parameters in luminal breast cancer

Discovery of novel KRAS‒PDEδ inhibitors with potent activity in patient-derived human pancreatic tumor xenograft models

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