HER2 expression on tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancer
Abstract Background Tumor-derived extracellular vesicles (tdEVs) and circulating tumor cells (CTCs) in the blood of metastatic cancer patients associate with poor outcomes. In this study, we explored the human epidermal growth factor receptor 2 (HER2) expression on CTCs and tdEVs of metastatic breas...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-08-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13058-020-01323-5 |
| _version_ | 1828892972598427648 |
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| author | Afroditi Nanou Leonie Laura Zeune Francois-Clement Bidard Jean-Yves Pierga Leonardus Wendelinus Mathias Marie Terstappen |
| author_facet | Afroditi Nanou Leonie Laura Zeune Francois-Clement Bidard Jean-Yves Pierga Leonardus Wendelinus Mathias Marie Terstappen |
| author_sort | Afroditi Nanou |
| collection | DOAJ |
| description | Abstract Background Tumor-derived extracellular vesicles (tdEVs) and circulating tumor cells (CTCs) in the blood of metastatic cancer patients associate with poor outcomes. In this study, we explored the human epidermal growth factor receptor 2 (HER2) expression on CTCs and tdEVs of metastatic breast cancer patients. Methods Blood samples from 98 patients (CLCC-IC-2006-04 study) were originally processed with the CellSearch® system using the CTC kit and anti-HER2 as an additional marker in the staining cocktail. CTCs and tdEVs were automatically enumerated from the generated CellSearch images using the open-source ACCEPT software. Results CTCs and tdEVs were subdivided based on their cytokeratin (CK) and HER2 phenotype into CK+HER2−, CK−HER2+, and CK+HER2+. The inclusion of anti-HER2 increased the percentage of informative samples with ≥ 1 detectable CTC from 89 to 95%. CK− CTCs and tdEVs correlated equally well with the clinical outcome as CK+ CTCs and tdEVs. Inter- and intra-patient heterogeneity was found for the CTC/tdEV phenotypes, and the presence of 2 or 3 classes of CTCs/tdEVs was associated with worse prognosis compared to a uniform CTC/tdEV phenotype present (1 class). The use of ≥ 7% HER2+CK+ tdEVs can predict HER2 expression of the tissue with 74% sensitivity and specificity using the HER2 amplification status of the primary tumor as a classification variable. Conclusions HER2 can be detected on CTCs and tdEVs not expressing CK, and these CK− CTCs/tdEVs have similar clinical relevance to CTCs and tdEVs expressing CK. tdEVs perform better than CTCs in predicting the HER2 status of the primary tissue. CTC and tdEV heterogeneity in the blood of patients is inversely associated with overall survival. |
| first_indexed | 2024-12-13T13:45:26Z |
| format | Article |
| id | doaj.art-082768ad69624a20b69b16e32cccb8ab |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-12-13T13:45:26Z |
| publishDate | 2020-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-082768ad69624a20b69b16e32cccb8ab2022-12-21T23:43:26ZengBMCBreast Cancer Research1465-542X2020-08-0122111110.1186/s13058-020-01323-5HER2 expression on tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancerAfroditi Nanou0Leonie Laura Zeune1Francois-Clement Bidard2Jean-Yves Pierga3Leonardus Wendelinus Mathias Marie Terstappen4Department of Medical Cell BioPhysics, Faculty of Science and Technology, University of TwenteDepartment of Medical Cell BioPhysics, Faculty of Science and Technology, University of TwenteDepartment of Medical Oncology, Institut Curie, PSL Research UniversityDepartment of Medical Oncology, Institut Curie, PSL Research UniversityDepartment of Medical Cell BioPhysics, Faculty of Science and Technology, University of TwenteAbstract Background Tumor-derived extracellular vesicles (tdEVs) and circulating tumor cells (CTCs) in the blood of metastatic cancer patients associate with poor outcomes. In this study, we explored the human epidermal growth factor receptor 2 (HER2) expression on CTCs and tdEVs of metastatic breast cancer patients. Methods Blood samples from 98 patients (CLCC-IC-2006-04 study) were originally processed with the CellSearch® system using the CTC kit and anti-HER2 as an additional marker in the staining cocktail. CTCs and tdEVs were automatically enumerated from the generated CellSearch images using the open-source ACCEPT software. Results CTCs and tdEVs were subdivided based on their cytokeratin (CK) and HER2 phenotype into CK+HER2−, CK−HER2+, and CK+HER2+. The inclusion of anti-HER2 increased the percentage of informative samples with ≥ 1 detectable CTC from 89 to 95%. CK− CTCs and tdEVs correlated equally well with the clinical outcome as CK+ CTCs and tdEVs. Inter- and intra-patient heterogeneity was found for the CTC/tdEV phenotypes, and the presence of 2 or 3 classes of CTCs/tdEVs was associated with worse prognosis compared to a uniform CTC/tdEV phenotype present (1 class). The use of ≥ 7% HER2+CK+ tdEVs can predict HER2 expression of the tissue with 74% sensitivity and specificity using the HER2 amplification status of the primary tumor as a classification variable. Conclusions HER2 can be detected on CTCs and tdEVs not expressing CK, and these CK− CTCs/tdEVs have similar clinical relevance to CTCs and tdEVs expressing CK. tdEVs perform better than CTCs in predicting the HER2 status of the primary tissue. CTC and tdEV heterogeneity in the blood of patients is inversely associated with overall survival.http://link.springer.com/article/10.1186/s13058-020-01323-5Circulating tumor cellsTumor-derived extracellular vesiclesHuman epidermal growth factor receptor 2HER2CellSearchACCEPT |
| spellingShingle | Afroditi Nanou Leonie Laura Zeune Francois-Clement Bidard Jean-Yves Pierga Leonardus Wendelinus Mathias Marie Terstappen HER2 expression on tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancer Breast Cancer Research Circulating tumor cells Tumor-derived extracellular vesicles Human epidermal growth factor receptor 2 HER2 CellSearch ACCEPT |
| title | HER2 expression on tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancer |
| title_full | HER2 expression on tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancer |
| title_fullStr | HER2 expression on tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancer |
| title_full_unstemmed | HER2 expression on tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancer |
| title_short | HER2 expression on tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancer |
| title_sort | her2 expression on tumor derived extracellular vesicles and circulating tumor cells in metastatic breast cancer |
| topic | Circulating tumor cells Tumor-derived extracellular vesicles Human epidermal growth factor receptor 2 HER2 CellSearch ACCEPT |
| url | http://link.springer.com/article/10.1186/s13058-020-01323-5 |
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