Laboratory validation studies in Ki-67 digital image analysis of breast carcinoma: a pathway to routine quality assurance

Wang, Morgan; McLaren, Sally; Jeyathevan, R.; Allanson, Benjamin; Ireland, Amanda; Kang, Alexandra; Meehan, Katie; Thomas, Carla; Robinson, Cleo; Combrinck, Marais; Harvey, Jennet; Sterrett, Gregory F.; Dessauvagie, Benjamin F.

doi:10.1016/j.pathol.2018.12.416

Cited by 7 publications

(5 citation statements)

References 28 publications

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“…33 In addition, our reported median Ki-67 of 6.5% is low compared to other studies. 34 However, in a previous report by co-authors, the reported DIA-Ki-67 threshold was 6.5%, this being the most robust and strongest prognosticator; which is in concordance with the present study. 16 Followup started 1 year after the time of diagnosis, therefore any recurrences within the first year are not recorded.…”

Section: Discussionsupporting

confidence: 94%

<p>Digital Image Analysis of Ki-67 Stained Tissue Microarrays and Recurrence in Tamoxifen-Treated Breast Cancer Patients</p>

Egeland¹,

Jónsdóttir²,

Lauridsen³

et al. 2020

CLEP

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The proliferation marker Ki-67 has been used as a prognostic marker to separate low-and high-risk breast cancer subtypes and guide treatment decisions for adjuvant chemotherapy. The association of Ki-67 with response to tamoxifen therapy is unclear. Highthroughput automated scoring of Ki-67 might enable standardization of quantification and definition of clinical cutoff values. We hypothesized that digital image analysis (DIA) of Ki-67 can be used to evaluate proliferation in breast cancer tumors, and that Ki-67 may be associated with tamoxifen resistance in early-stage breast cancer. Patients and Methods: Here, we apply DIA technology from Visiopharm using a custom designed algorithm for quantifying the expression of Ki-67, in a case-control study nested in the Danish Breast Cancer Group clinical database, consisting of stages I, II, or III breast cancer patients of 35-69 years of age, diagnosed during 1985-2001, in the Jutland peninsula, Denmark. We assessed DIA-Ki-67 score on tissue microarrays (TMAs) from breast cancer patients in a case-control study including 541 ER-positive and 300 ER-negative recurrent cases and their non-recurrent controls, matched on ER-status, cancer stage, menopausal status, year of diagnosis, and county of residence. We used logistic regression to estimate odds ratios and associated 95% confidence intervals to determine the association of Ki-67 expression with recurrence risk, adjusting for matching factors, chemotherapy, type of surgery, receipt of radiation therapy, age category, and comorbidity. Results: Ki-67 was not associated with increased risk of recurrence in tamoxifen-treated patients (ORadj =0.72, 95% CI 0.54, 0.96) or ER-negative patients (ORadj =0.85, 95% CI 0.54, 1.34). Conclusion: Our findings suggest that Ki-67 digital image analysis in TMAs is not associated with increased risk of recurrence among tamoxifen-treated ER-positive breast cancer or ER-negative breast cancer patients. Overall, our findings do not support an increased risk of recurrence associated with Ki-67 expression.

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Section: Discussionsupporting

confidence: 94%

<p>Digital Image Analysis of Ki-67 Stained Tissue Microarrays and Recurrence in Tamoxifen-Treated Breast Cancer Patients</p>

Egeland¹,

Jónsdóttir²,

Lauridsen³

et al. 2020

CLEP

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“…Histological grade and the proliferative marker Ki-67 are important variables for the risk classification of early breast cancer. Both variables, however, have considerable inter-laboratory and -observer variability [26,27]. Therefore, it is not surprising that, similar to other reports, the additional gene expression analysis is most often used in tumors of intermediate histological grade [23] and intermediate Ki-67.…”

Section: Discussionmentioning

confidence: 70%

EndoPredict® in early hormone receptor-positive, HER2-negative breast cancer

Almstedt

Mendoza

Otto³

et al. 2020

Breast Cancer Res Treat

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Purpose Evaluating consecutive early breast cancer patients, we analyzed both the impact of EndoPredict ® on clinical decisions as well as clinico-pathological factors influencing the decision to perform this gene expression test. Methods Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative early breast cancer patients treated between 2011 and 2016 were included in this study to investigate the role of EndoPredict ® (EPclin) in the treatment of early breast cancer. A main study aim was to analyze the changes in therapy recommendations with and without EPclin. In addition, the impact of clinico-pathological parameters for the decision to perform EPclin was examined by Pearson's chi-squared test (χ 2-test) and Fisher's exact test as well as univariate and multivariate logistic regressions. Results In a cohort of 869 consecutive early HR-positive, HER-negative breast cancer patients, EPclin was utilized in 156 (18.0%) patients. EPclin led to changes in therapy recommendations in 33.3% (n = 52), with both therapy escalation in 19.2% (n = 30) and de-escalation in 14.1% (n = 22). The clinico-pathological factors influencing the use of EPclin were age (P < 0.001, odds ratio [OR] 0.498), tumor size (P = 0.011, OR 0.071), nodal status (P = 0.021, OR 1.674), histological grade (P = 0.043, OR 0.432), and Ki-67 (P < 0.001, OR 3.599). Conclusions EPclin led to a change in therapy recommendations in one third of the patients. Clinico-pathological parameters such as younger age, smaller tumor size, positive nodal status, intermediate histological grade and intermediate Ki-67 had a significant influence on the use of EndoPredict ® .

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“…Geniş bir meme kanseri kohortunda (1951 vaka) en yüksek Ki67 değeri triplenegatif alt tipte, sonra HER2+ alt tipte ve ardından lüminal B alt tipte gözlenmiştir 14 Çalışmada DGA ve MD Ki67 sayımları arasında çok yüksek korelasyon ve Bland Altman analizinde iki sayım farkını sıfıra yakın gözlemlenmiştir. Bu bulgular, eşdeğer ileri seviyelerde olmasa da yüksek korelasyonlar göstermiş araştırmalar ile paraleldir 2,16 . Ancak aynı düzeyde yüksek korelasyon bildirmemiş gözlemler de vardır 3,17 .…”

Section: Discussionunclassified

Comparison of Ki67 Index Measurements in Breast Cancer with Manual and Digital Methods

SİLAV

2023

İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi

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Amaç: Meme kanserinde immunhistokimyasal biyobelirteç olarak umut vaat eden Ki67 proteini, mitoz döngüsünün tüm aktif fazlarında bulunduğundan hücre proliferasyon değerlendirmelerinde kullanılır. Ki67 indeksi meme kanserli hastalarda prediktif ve prognostik değerdedir. Manuel değerlendirme (MD) ile Ki67 sayımı gözlemciler arası değişkenliğe hassas ve zaman alıcıdır. Son yıllarda, dijital görüntü analizinin (DGA) Ki67 ölçümleri için hızlı ve objektif olduğunu belirten çalışmalar artmaktadır ancak bu yöntemin rutin uygulamaya girmesi ileri çalışmaları gerektirmektedir. Bu araştırmada 85 invaziv meme kanseri vakasında MD, DGA ve GK (göz kararı) Ki67 ölçümlerini kıyaslanmıştır. Yöntem: Tümör moleküler tipleri, mitoz sayıları, GK, MD ve DGA ile ölçülmüş Ki67 değerleri ve korelasyonları saptandı. DGA analizleri ViraPath (Virasoft Yazılım, İstanbul, Türkiye) yazılımıyla, parametreler arasında istatistik korelasyonlar NCSS (Number Cruncher Statistical System, 2020) ile incelendi. Bulgular: Her üç farklı metotla belirlenmiş Ki67 indeks değerlerinin yaş, histolojik derece, mitoz sayıları ve moleküler tip açısından korelasyon ve farklılıkları literatür ile uyumlu bulundu. DGA ve MD ile sayılmış Ki67 indeksleri arasında sınıf içi korelasyon katsayısı 0,974 olarak ölçüldü ve Bland Altman analizleri ile MD ve DGA sayımları arasındaki fark sıfıra yakın saptandı. Sonuç: DGA sayımları MD’nin yerini alacak güvenilirlikte sonuçlar vermektedir. Çok merkezli ve metot standartlarını optimize edecek çalışmalarla patoloji pratiğine zamansal katkı ve yüksek hassasiyet kazandırılabilir.

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Laboratory validation studies in Ki-67 digital image analysis of breast carcinoma: a pathway to routine quality assurance

Cited by 7 publications

References 28 publications

<p>Digital Image Analysis of Ki-67 Stained Tissue Microarrays and Recurrence in Tamoxifen-Treated Breast Cancer Patients</p>

<p>Digital Image Analysis of Ki-67 Stained Tissue Microarrays and Recurrence in Tamoxifen-Treated Breast Cancer Patients</p>

EndoPredict® in early hormone receptor-positive, HER2-negative breast cancer

Comparison of Ki67 Index Measurements in Breast Cancer with Manual and Digital Methods

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