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. 2022 Jan 3;2(1):7-14.
doi: 10.21873/cdp.10070. eCollection 2022 Jan-Feb.

Visual Counting and Automated Image-analytic Assessment of Ki-67 and their Prognostic Value in Synovial Sarcoma

Riikka E Laurila  1 , Tom O Böhling  2 , Carl P Blomqvist  3   4 , Christina Karlsson  4 , Erkki J Tukiainen  5 , Jussi Repo  6 , Mika M Sampo  1
Affiliations

Visual Counting and Automated Image-analytic Assessment of Ki-67 and their Prognostic Value in Synovial Sarcoma

Riikka E Laurila et al. Cancer Diagn Progn. .

Abstract

Background: Ki-67 is a widely used proliferation marker reflecting prognosis in various tumors. However, visual assessment and scoring of Ki-67 suffers from marked inter-observer and intra-observer variability. We aimed to assess the concordance of manual counting and automated image-analytic scoring methods for Ki-67 in synovial sarcoma.

Patients and methods: Tissue microarrays from 34 patients with synovial sarcoma were immunostained for Ki-67 and scored both visually and with 3DHistech QuantCenter.

Results: The automated assessment of Ki-67 expression was in good agreement with the visually counted Ki-67 (r Pearson =0.96, p<0.001). In a Cox regression model automated [hazard ratio (HR)=1.047, p=0.024], but not visual (HR=1.063, p=0.053) assessment method associated high Ki-67 scores with worse overall survival.

Conclusion: The automated Ki-67 assessment method appears to be comparable to the visual method in synovial sarcoma and had a significant association to overall survival.

Keywords: Ki-67; Ki-67 antigen; Sarcoma; automated; pattern recognition; survival analysis; synovial; visual counting method.

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Conflict of interest statement

The Authors declare that there are no conflicts of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1. Example of a TMA spot image with two annotations.
Figure 2
Figure 2. Bland-Altman scatterplot of agreement between visual counting versus automated counting. Mean: 2.15%, 95% CI=-6.14%-10.44%.
Figure 3
Figure 3. The four cases with the largest Ki-67 differences between the two methods. In picture 1, the automatically assessed Ki-67 index is very high (66.12%). The number of negative nuclei is relatively small and some of the overlapping nuclei are counted as one resulting in overestimation of the positivity index. In picture 2, the nuclei are packed densely and the frontally oriented cells appear small-sized. In picture 3, there is extracellular staining and some of the negative nuclei have slightly blurred contours. In picture 4, sagittally oriented cells have fusiform morphology and are not easily segmented.
Figure 4
Figure 4. Survival curves by Ki-67 tertiles. Survival curves for the automated assessment method of the three Ki-67 subgroups: low<3.2%, moderate 3.2-14%, high>14.7% and for the visual assessment method: low<2.5%, moderate 2.5-11.3%, high>11.3%. The high tertile is illustrated with a thick line, the moderate with a thin line, and the low with a stippled line.
See this image and copyright information in PMC

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