Visual assessment of Ki67 at a glance is an easy method to exclude many luminal-type breast cancers from counting 1000 cells

Hida, Akira I.; Oshiro, Yumi; Inoue, Hiromichi; Kawaguchi, Hidetoshi; Yamashita, Natsumi; Moriya, Takuya

doi:10.1007/s12282-013-0460-8

Cited by 25 publications

(22 citation statements)

References 26 publications

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“…in the range of Ki67 LI 10-30 % [3]. A visual scoring methodology proposed by Hida et al, might be used as method of choice for “low” (Ki67 LI <10 %) or “high” (Ki67 LI >30 %) proliferatively active cases, leaving behind “grey zone” cases, which requires more precise methodologies [34]. …”

Section: Discussionmentioning

confidence: 99%

Impact of tissue sampling on accuracy of Ki67 immunohistochemistry evaluation in breast cancer

et al. 2016

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BackgroundGene expression studies have identified molecular subtypes of breast cancer with implications to chemotherapy recommendations. For distinction of these types, a combination of immunohistochemistry (IHC) markers, including proliferative activity of tumor cells, estimated by Ki67 labeling index is used. Clinical studies are frequently based on IHC performed on tissue microarrays (TMA) with variable tissue sampling. This raises the need for evidence-based sampling criteria for individual IHC biomarker studies. We present a novel tissue sampling simulation model and demonstrate its application on Ki67 assessment in breast cancer tissue taking intratumoral heterogeneity into account.MethodsWhole slide images (WSI) of 297 breast cancer sections, immunohistochemically stained for Ki67, were subjected to digital image analysis (DIA). Percentage of tumor cells stained for Ki67 was computed for hexagonal tiles super-imposed on the WSI. From this, intratumoral Ki67 heterogeneity indicators (Haralick’s entropy values) were extracted and used to dichotomize the tumors into homogeneous and heterogeneous subsets. Simulations with random selection of hexagons, equivalent to 0.75 mm circular diameter TMA cores, were performed. The tissue sampling requirements were investigated in relation to tumor heterogeneity using linear regression and extended error analysis.ResultsThe sampling requirements were dependent on the heterogeneity of the biomarker expression. To achieve a coefficient error of 10 %, 5–6 cores were needed for homogeneous cases, 11–12 cores for heterogeneous cases; in mixed tumor population 8 TMA cores were required. Similarly, to achieve the same accuracy, approximately 4,000 nuclei must be counted when the intratumor heterogeneity is mixed/unknown. Tumors of low proliferative activity would require larger sampling (10–12 TMA cores, or 6,250 nuclei) to achieve the same error measurement results as for highly proliferative tumors.ConclusionsOur data show that optimal tissue sampling for IHC biomarker evaluation is dependent on the heterogeneity of the tissue under study and needs to be determined on a per use basis. We propose a method that can be applied to determine the sampling strategy for specific biomarkers, tissues and study targets. In addition, our findings highlight the benefit of high-capacity computer-based IHC measurement techniques to improve accuracy of the testing.Electronic supplementary materialThe online version of this article (doi:10.1186/s13000-016-0525-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Impact of tissue sampling on accuracy of Ki67 immunohistochemistry evaluation in breast cancer

et al. 2016

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“…We recently showed that visual assessment of Ki67 at a glance with a 10-grade scale (Eye-10) is easy and can help classify luminal-type breast cancers 5. Here, we have modified it into a simpler 5-grade scale, Eye-5.…”

Section: Discussionmentioning

confidence: 99%

“…Fixation and IHC staining on representative blocks of each tumour was performed as previously described 5. Ki67 antibody (MIB-1, 1:100) was from DAKO (Glostrup, Denmark).…”

Section: Methodsmentioning

confidence: 99%

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Visual assessment of Ki67 using a 5-grade scale (Eye-5) is easy and practical to classify breast cancer subtypes with high reproducibility

et al. 2015

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“…A study by Akira I. Hida et al showed a significant positive correlation between Eye-10 and Ki67LI with the magnitude of (r=0.94). They showed that the visual assessment of Ki67 at a glance with a 10-grade scale (Eye-10) is an easy method (a rational alternative for Ki67LI) and can exclude obviously high and low Ki67 breast tumors, leaving a gray zone around a cut-off point (5).…”

Section: Discussionmentioning

confidence: 99%

Assessment of Ki67 in Breast Cancer: A Comparison Between the Eye-10 Method, Stepwise Counting Strategy, and International System of Ki67 Evaluation

Kadivar¹,

Aram²

2020

Iran J Pathol

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Scan to discover online Background & Objective: Ki-67 evaluation is an essential tool to define luminal A and B breast cancers, which is not yet systematized. The International Ki67 in Breast Cancer Working Group suggests the counting of 500 or 1000 cancer cells, which is a time-consuming process. Therefore, novel methods, such as the Eye-10 method and stepwise counting strategy, are proposed to facilitate measurement. Methods: Immunohistochemical staining of Ki67 was performed on 100 hormonereceptor-positive invasive ductal carcinoma specimens. Ki67LI was evaluated for each case, and then results were dichotomized by a cutoff point of 20%. Next, for each sample, an expert pathologist visually assessed percentages of Ki67-positive cells in 10% intervals at a glance (Eye-10 method). Finally, by using a dynamic process with rejection regions, Ki67 was defined so if the estimate belonged to the upper or lower rejection region, the Ki67 status had been determined and if the rejection region could not be reached after counting the maximum number of 400 tumor cells, the specimen was regarded as equivocal (stepwise counting strategy). Results: The comparison between Eye-10 and Ki67LI revealed almost perfect agreement (kappa coefficient =0.889), and the concordance between the stepwise counting strategy and Ki67LI was substantial (kappa coefficient =0.639). Conclusion: Both two methods left some results in the gray/intermediate zone, which is unavoidable. Both methods are much faster and simpler than evaluation of Ki67LI and are also reliable. Regarding the gray zone in both methods, further improvements in the methodology, as well as more analytical studies, are needed.

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Visual assessment of Ki67 at a glance is an easy method to exclude many luminal-type breast cancers from counting 1000 cells

Cited by 25 publications

References 26 publications

Impact of tissue sampling on accuracy of Ki67 immunohistochemistry evaluation in breast cancer

Impact of tissue sampling on accuracy of Ki67 immunohistochemistry evaluation in breast cancer

Visual assessment of Ki67 using a 5-grade scale (Eye-5) is easy and practical to classify breast cancer subtypes with high reproducibility

Assessment of Ki67 in Breast Cancer: A Comparison Between the Eye-10 Method, Stepwise Counting Strategy, and International System of Ki67 Evaluation

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