Distribution pattern of the Ki67 labelling index in breast cancer and its implications for choosing cut-off values

Cserni, Gábor; Vörös, A.; Liepniece-Karele, Inta; Bianchi, Simonetta; Vezzosi, Vania; Grabau, Dorthe; Sapino, Anna; Castellano, Isabella; Regitnig, Peter; Foschini, Maria Pia; Zolota, Vassiliki; Varga, Zsuzsanna; Figueiredo, Paulo; Decker, Thomas; Focke, CM; Kulka, Janina; Kaya, Hakan; Reiner-Concin, Angelika; Amendoeira, Isabel; Callagy, Grace; Caffrey, Emer; Wesseling, Jelle; Wells, Clive

doi:10.1016/j.breast.2014.02.003

Cited by 59 publications

(51 citation statements)

References 15 publications

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“…Assessment of the overall Ki67 expression including HS and LS and areas in between is called average score. Currently no consensus for Ki67 staining evaluation whether it should only consider the HS if present, take the average score including HS or avoiding them completely [23] and comparable study assessing different scoring methods is needed.…”

Section: Discussionmentioning

confidence: 99%

“…Such heterogeneity could be a gradient of increasing Ki67 positivity toward the tumour edge and or Ki67 variable expressivity anywhere in the tumour in the form of hot spots [23,24]. To ensure satisfactory reproducibility when using Ki67 IHC in research purposes and in the way of it inclusion into routine clinical practice for BC, it is still debatable whether to score the hot spots of expression or the average expression.…”

Section: Introductionmentioning

confidence: 99%

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Impact of intratumoural heterogeneity on the assessment of Ki67 expression in breast cancer

Aleskandarany

Green

Ashankyty

et al. 2016

Breast Cancer Res Treat

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In breast cancer (BC), the prognostic value of Ki67 expression is well-documented.Intratumoural heterogeneity (ITH) of Ki67 expression is amongst the several technical issues behind the lag of its inclusion into BC prognostic work-up. The immunohistochemical (IHC) expression of anti-Ki67 antibody (MIB1 clone) was assessed in four full-face (FF) sections from different primary tumour quadrants and their matched axillary nodal (LN) metastases in a series of 55 BC. Assessment was made using the highest expression (hot) spots (HS), lowest expression (LS), and overall/average expression scores (AS) in each section. Heterogeneity score (Hes), coefficient of variation and correlation coefficient were used to assess the levels of Ki67 ITH. Ki67 HS, LS, and AS scores were highly variable within the same section and between different sections of the primary tumour, with maximal variation observed in the LS (p<0.001). The least variability between the different slides was observed with HS scoring. Although the associations between Ki67 and clinicopathological and molecular variables were similar when using HS or AS, the best correlation between AS and HS was observed in tumours with high Ki67 expression only. Ki67 expression in LN deposits was less heterogeneous than in the primary tumours and was perfectly correlated with the HS Ki67 expression in the primary tumour sections (r=0.98, p <0.001). In summary, assessment of Ki67 expression using HS scoring method on a fullface BC tissue section can represent the primary tumour growth fraction that likely to metastasise. The association between Ki67 expression pattern in the LN metastasis and the HS in the primary tumour may reflect the temporal heterogeneity through clonal expansion.3

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of intratumoural heterogeneity on the assessment of Ki67 expression in breast cancer

Aleskandarany

Green

Ashankyty

et al. 2016

Breast Cancer Res Treat

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“…Many cut-offs values may work virtually equally well for prognostic purposes in a particular cohort. This does not necessarily indicate that they would equally well work in other population or when examined by other investigators or with different methodology [39,85,86]. Moreover, cut-off points should depend on clinical context, for example for prognostic purposed or for prediction of response of particular therapy protocol [39,42], or for monitoring disease progression.…”

Section: Cut-off Value For G1/g2 Distinctionmentioning

confidence: 99%

“…Human factor is critical for Ki67 LI assessment, not only for eyeballed estimates, but also for formal manual counting [39,56,86]. Important issue for manual counting is HS recognition, as discussed above.…”

Section: Human Factormentioning

confidence: 99%

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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“…This suggests that the simple approach of estimating by eyeballing has also diagnostic value, and may be better received by the pathological society as a simple and fast method, taking 4 to 12 times less time than counting [39,46]. The daily use of estimating rather than counting the Ki-67 LI by at least some pathologists was also highlighted in the series evaluating the distribution of Ki-67 LI values in different pathology departments [47].…”

Section: Discussionmentioning

confidence: 99%

Various Aspects of Ki-67 Immunohistochemistry Determined Proliferation in Breast Cancer

Vörös

Self Cite

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Distribution pattern of the Ki67 labelling index in breast cancer and its implications for choosing cut-off values

Cited by 59 publications

References 15 publications

Impact of intratumoural heterogeneity on the assessment of Ki67 expression in breast cancer

Impact of intratumoural heterogeneity on the assessment of Ki67 expression 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

Various Aspects of Ki-67 Immunohistochemistry Determined Proliferation in Breast Cancer

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