HER-2 status of circulating tumor cells in a metastatic breast cancer cohort: A comparative study on characterization techniques

Autor: Luc Dirix, Bram De Laere, Steven Van Laere, Jasper Van Haver, Dieter Peeters, Peter A. van Dam, Marc Peeters, Ellen Sluydts, Jaco Kraan, Anja Brouwer, Ali El Moussaoui, Pauline A J Mendelaar
Přispěvatelé: Medical Oncology
Rok vydání: 2019
Předmět:
0301 basic medicine
Receptor
ErbB-2
Gene Expression
Metastasis
Workflow
White Blood Cells
0302 clinical medicine
Circulating tumor cell
Animal Cells
Gene duplication
Breast Tumors
Basic Cancer Research
Medicine and Health Sciences
Medicine
In Situ Hybridization
Fluorescence
Multidisciplinary
Neoplastic Cells
Circulating
Metastatic breast cancer
Oncology
030220 oncology & carcinogenesis
Biomarker (medicine)
Female
Cellular Types
Engineering sciences. Technology
Research Article
Imaging Techniques
Immune Cells
Science
Immunology
Breast Neoplasms
In situ hybridization
Image Analysis
Research and Analysis Methods
03 medical and health sciences
Breast cancer
SDG 3 - Good Health and Well-being
Cell Line
Tumor
Breast Cancer
Fluorescence Imaging
Biomarkers
Tumor
Genetics
Humans
RNA
Messenger
Blood Cells
business.industry
Gene Amplification
Biology and Life Sciences
Cancers and Neoplasms
Cell Biology
medicine.disease
030104 developmental biology
Metastatic Tumors
Cell culture
Cancer research
business
Zdroj: PLoS One (print), 14(9):e0220906. Public Library of Science
PLoS ONE, Vol 14, Iss 9, p e0220906 (2019)
PLoS ONE
ISSN: 1932-6203
Popis: textabstractBackground Personalized targeted treatment in metastatic breast cancer relies on accurate assessment of molecular aberrations, e.g. overexpression of Human Epidermal growth factor Receptor 2 (HER-2). Molecular interrogation of circulating tumor cells (CTCs) can provide an attractive alternative for real-time biomarker assessment. However, implementation of CellSearch-based HER-2 analysis has been limited. Immunofluorescent (IF) image interpretation is crucial, as different HER-2 categories have been described. Major questions in CTC research are how these IF categories reflect gene expression and amplification, and if we should consider ‘medium’ HER-2 expressing CTCs for patient selection. Methods Tumor cells from spiked cell lines (n = 8) and CTCs (n = 116 samples) of 85 metastatic breast cancer patients were enriched using CellSearch. Comparative analysis of HER-2 expression by IF imaging (ACCEPT, DEPArray, and visual scoring) with qRT-PCR and HER-2/neu FISH was performed. Results Automated IF HER-2-profiling by DEPArray and ACCEPT delivered comparable results. There was a 98% agreement between 17 trained observers (visual scoring) and ACCEPT considering HER-2neg and HER-2high expressing CTCs. However, 89% of HER-2med expressing CTCs by ACCEPT were scored negative by observers. HER-2high expressing tumor cells demonstrated HER-2/neu gene amplification, whereas HER-2neg and HER-2med expressing tumor cells and CTCs by ACCEPT were copy-number neutral. All patients with HER-2-positive archival tumors had �1 HER-2high expressing CTCs, while 80% of HER-2- negative patients did not. High relative gene expression of HER-2 measured on enriched CTC lysates correlated with having �1 HER-2high expressing CTCs. Conclusion Automated images analysis has enormous potential for clinical implementation. HER-2 characterization and clinical trial design should be focused on HER-2high expressing CTCs.
Databáze: OpenAIRE
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