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Quantifying HER-2 expression on circulating tumor cells by ACCEPT
Leonie Zeune1,2, Guus van Dalum2, Charles Decraene3,4
1Department of Applied Mathematics, MIRA Institute, University of Twente, Enschede, The Netherlands.
Abstract:
Circulating tumor cells (CTCs) isolated from blood can be probed for the expression of treatment targets. Immunofluorescence is often used for both the enumeration of CTC and the determination of protein expression levels related to treatment targets. Accurate and reproducible assessment of such treatment target expression levels is essential for their use in the clinic. To enable this, an open source image analysis program named ACCEPT was developed in the EU-FP7 CTCTrap and CANCER-ID programs. Here its application is shown on a retrospective cohort of 132 metastatic breast cancer patients from which blood samples were processed by CellSearch® and stained for HER-2 expression as additional marker. Images were digitally stored and reviewers identified a total of 4084 CTCs. CTC's HER-2 expression was determined in the thumbnail images by ACCEPT. 150 of these images were selected and sent to six independent investigators to score the HER-2 expression with and without ACCEPT. Concordance rate of the operators' scoring results for HER-2 on CTCs was 30% and could be increased using the ACCEPT tool to 51%. Automated assessment of HER-2 expression by ACCEPT on 4084 CTCs of 132 patients showed 8 (6.1%) patients with all CTCs expressing HER-2, 14 (10.6%) patients with no CTC expressing HER-2 and 110 (83.3%) patients with CTCs showing a varying HER-2 expression level. In total 1576 CTCs were determined HER-2 positive. We conclude that the use of image analysis enables a more reproducible quantification of treatment targets on CTCs and leads the way to fully automated and reproducible approaches.
Insights
An open-source image analysis tool, ACCEPT, improved the reproducible quantification of HER-2 expression on circulating tumor cells (CTCs). This advancement is crucial for using CTCs as biomarkers in metastatic breast cancer treatment.
Area of Science:
- Biomedical Engineering
- Oncology
- Medical Imaging Analysis
Background:
- Circulating tumor cells (CTCs) are valuable biomarkers for monitoring cancer progression and treatment response.
- Accurate assessment of treatment target expression on CTCs is essential for personalized medicine.
- Current methods for quantifying target expression on CTCs can lack reproducibility.
Purpose of the Study:
- To evaluate the utility of the open-source image analysis program ACCEPT for quantifying HER-2 expression on CTCs.
- To assess the impact of ACCEPT on the reproducibility of HER-2 scoring by independent investigators.
- To determine the prevalence of HER-2 expression in CTCs from metastatic breast cancer patients.
Main Methods:
- Development and application of the ACCEPT image analysis tool for quantifying HER-2 on CTCs.
- Retrospective analysis of 132 metastatic breast cancer patients' blood samples processed by CellSearch®.
- Comparison of HER-2 scoring concordance with and without ACCEPT among six independent investigators.
Main Results:
- The concordance rate for HER-2 scoring on CTCs increased from 30% to 51% when using the ACCEPT tool.
- Automated assessment by ACCEPT revealed varying HER-2 expression levels across CTCs in 83.3% of patients.
- Out of 4084 identified CTCs, 1576 were determined to be HER-2 positive.
Conclusions:
- Image analysis tools like ACCEPT significantly enhance the reproducibility of quantifying treatment targets on CTCs.
- ACCEPT facilitates a more standardized and potentially automated approach for CTC biomarker analysis.
- This technology holds promise for advancing the clinical utility of CTCs in precision oncology.
