Comparison of the effect of different techniques for measurement of Ki67 proliferation on reproducibility and prognosis prediction accuracy in breast cancer

Gudlaugsson, Einar; Skaland, Ivar; Janssen, Emiel A. M.; Smaaland, Rune; Shao, Zhi‐Ming; Malpica, Anaís; Voorhorst, Feja J.; Baak, J. P. A.

doi:10.1111/j.1365-2559.2012.04329.x

Cited by 119 publications

(127 citation statements)

References 16 publications

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“…Therefore, the standardization of Ki67 assessment is considered more crucial because of its values in clinical practice. However, Ki67 LI measurements by immunohistochemical analysis lack interobserver and interlaboratory reproducibility [9][10][11][12][13]. Currently, there is still no global guideline, with both reproducibility and objective standardization, has been established for Ki67 LI assessment.…”

Section: Introductionmentioning

confidence: 99%

An interobserver reproducibility analysis of ki67 visual assessment in breast cancer

Shui

et al. 2016

Pathology

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Section: Introductionmentioning

confidence: 99%

An interobserver reproducibility analysis of ki67 visual assessment in breast cancer

Shui

et al. 2016

Pathology

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“…Density of cells in particular tumor area may also influence selection of this area as HS [75]. HS selection is done subjectively and results of these choices (at least in breast cancer) do not necessarily correlated with HS recognized using digital image analysis [73,74]. Automated HS detection may be an alternative [74,76,77,79,80].…”

Section: Hot Spotsmentioning

confidence: 99%

“…Important issue for manual counting is HS recognition, as discussed above. Another critical issue of Ki67 LI is a subjective threshold of stain intensity, which is enough to score a particular nucleus as positive [53,73]. Interestingly, inter-observer variability in scoring breast cancer samples cannot be fully explained by technique of scoring (estimation vs. counting), HS selection, positivity threshold or IHC technique [56].…”

Section: Human Factormentioning

confidence: 99%

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Tissue heterogeneity contributes to suboptimal precision of WHO 2010 scoring criteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreascriteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreas

Liszka¹

2016

pjp

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Reporting of Ki67 labeling index (LI) is a routine in diagnostics of neuroendocrine neoplasms of the pancreas. The aim of the study was to examine whether heterogeneity of Ki67 LI distribution in primary tumoral tissue influences precision of reporting of Ki67 LI and Ki67-LI-based grade, both established in adherence to WHO 2010 guidelines. Seventy-one samples of neuroendocrine tumours (NET) and 6 samples of neuroendocrine carcinomas (NEC) of the pancreas were taken for manual counting of Ki67 LI in 25 portions of 100 cells (2500 cells in total) in 3 hot spots an in a single area of lower proliferation rate (cold spot) in each case. Both NET and NEC showed Ki67 LI heterogeneity within primary tumour. Almost 20% of NET showed higher grade when 500 cells rather than 2000 cells were counted in hot spot area. Suboptimal choice of hot spot resulted in under-grading of approximately 20% of NET. Cold spots were constantly present in NET. Heterogeneity of Ki67 LI was also present in NEC, but it virtually never resulted in under-grading. Concept and methodology of Ki67 LI counting in neuroendocrine neoplasms of the pancreas requires clarification. Efforts aiming to improve precision of assessment of Ki67 LI are needed.

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“…The results showed that counts of Ki67 positive cells by different pathologists were poorly reproducible. Interactive point-weighted counting of Ki67 by morphometric techniques were much more reproducible, but automated digital image analysis (DIA) was the most reproducible and prognostically strongest [9].…”

Section: Introductionmentioning

confidence: 99%

Prognostic comparison of the proliferation markers mitotic activity index, phosphohistone H3, Ki67, steroid receptors, HER2, high molecular weight cytokeratins and classical prognostic factors in T 1-2 N 0 M 0 breast cancer

Gudlaugsson

Kłos

Skaland

et al. 2013

pjp

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The proliferation factors: mitotic activity index (MAI), phosphohistone H3 (PPH3) and Ki67 have strong prognostic value in early breast cancer but their independent value to each other and other prognostic factors has not been evaluated. In 237 T 1-2 N 0 M 0 breast cancers without systemic adjuvant treatment, formalized MAI assessment and strictly standardized, fully automated quantitative immunohistochemistry (IHC) for Ki67, PPH3, estrogen (ER) and progesterone receptor (PR), HER2, cytokeratins-5/6 and -14, and automated digital image analysis (DIA) for measuring PPH3 and Ki67 were performed. Section thickness was measured to further control IHC measurements. All features were measured in the periphery of tumors. The different proliferation assessments and other well-established clinicopathological and biomarker prognostic factors were compared. DIA-Ki67 added prognostically to PPH3. None of the other biomarkers or clinicopathological variables added prognostically to this PPH3/Ki67 combination. However, when PPH3 is replaced by MAI the prognostic value is nearly the same. In early operable node negative breast cancer without adjuvant systemic treatment, Ki67 with a threshold of 6.5% assessed by digital image analysis in the periphery of the tumor is prognostically strong. The combination of either PPH3/Ki67 or MAI/Ki67 overshadowed the prognostic value of all other features including Ki67 alone.

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Comparison of the effect of different techniques for measurement of Ki67 proliferation on reproducibility and prognosis prediction accuracy in breast cancer

Abstract: In node-negative breast cancer without adjuvant systemic treatment, Ki67% by DIA, but not subjective counts, is reproducible and prognostically strong. This casts serious doubt on therapeutic guidelines using subjective counts of Ki67.

Cited by 119 publications

References 16 publications

An interobserver reproducibility analysis of ki67 visual assessment in breast cancer

An interobserver reproducibility analysis of ki67 visual assessment in breast cancer

Tissue heterogeneity contributes to suboptimal precision of WHO 2010 scoring criteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreascriteria for Ki67 labeling index in a subset of neuroendocrine neoplasms of the pancreas

Prognostic comparison of the proliferation markers mitotic activity index, phosphohistone H3, Ki67, steroid receptors, HER2, high molecular weight cytokeratins and classical prognostic factors in T 1-2 N 0 M 0 breast cancer

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