The commentary by Nielsen et al. (1) summarized over a decade of efforts by a group of dedicated oncologists (the International Ki67 in breast cancer Working Group [IKWG]) attempting to standardize immunohistochemistry (IHC)–based Ki67 assessment in daily clinical practice. A key recommendation in the commentary is that “in this T1-2, N0-1 patient group, the IKWG consensus is that Ki67 5% or less, or 30% or more, can be used to estimate prognosis.”
We replotted the results reported in figure 4a of a previous paper published by the same IKWG, showing independent assessment of the same 30 IHC slides from 22 different pathological laboratories (2) (Figure 1). The “5% or less, or 30% or more” recommendation was applied in the scatterplot by covering the space between 5% and 30% with a box. Clearly, there remains a lot of equivocal cases even after this recommendation is applied. In fact, consensus may be reached in only 4 out of 30 IHC slides.
Figure 1.
The heat map of Ki67 scores in figure 4a from Leung et al. (2) was replotted based on the reported Ki67 scores. Each dot represented a Ki67 score from a pathological lab. There were 30 immunohistochemistry (IHC) slides, as indicated on the x-axis. For each slide, there were 22 Ki67 scores from independent pathological laboratories. The lower and upper sides of the box were 5% and 30% Ki67 scores, respectively. The covered area indicated those Ki67 scores not recommended to be used for prognosis by the International Ki67 in breast cancer Working Group (IKWG).
The IHC has been and will continue to be an indispensable part of clinical diagnostics. However, this is an inherent qualitative assay, never meant to be quantitative (3). This situation is unlikely to be improved by automatic scoring as suggested in the commentary, as it too is unable to convert a qualitative image into a quantitative result. Continuing efforts in this direction for Ki67 assessment would most likely be a waste of public resources.
Alternative Ki67 detection methods should be actively pursued (2,4-6), so objective and quantitative assessment of Ki67 protein levels can be realized in daily clinical practice to benefit millions of cancer patients worldwide.
Funding
None.
Notes
Role of the funder: Not applicable.
Disclosures: JZ and MY are employees of Quanticision Diagnostics, Inc, who has developed the Quantitative Dot Blot (QDB) method for objective quantitation of Ki67 protein levels for clinical diagnostics.
Author contributions: Conceptualization: JZ and MY. Visualization & Writing—original draft, JZ. Writing—review & editing: JZ and MY.
Data Availability
No new data were used or generated for this correspondence.
References
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Data Availability Statement
No new data were used or generated for this correspondence.