Multi-Parameter Analysis of Disseminated Tumor Cells (DTCs) in Early Breast Cancer Patients with Hormone-Receptor-Positive Tumors

Theresa König; Senol Dogan; Anne Kathrin Höhn; Laura Weydandt; Bahriye Aktas; Ivonne Nel

doi:10.3390/cancers15030568

Multi-Parameter Analysis of Disseminated Tumor Cells (DTCs) in Early Breast Cancer Patients with Hormone-Receptor-Positive Tumors

Cancers (Basel). 2023 Jan 17;15(3):568. doi: 10.3390/cancers15030568.

Authors

Theresa König¹, Senol Dogan¹, Anne Kathrin Höhn², Laura Weydandt¹, Bahriye Aktas¹, Ivonne Nel¹

Affiliations

¹ Department of Gynecology, Medical Center, University of Leipzig, 04103 Leipzig, Germany.
² Department of Pathology, Medical Center, University of Leipzig, 04103 Leipzig, Germany.

Abstract

Background: Patients with hormone-receptor-positive (HR+) breast cancer are at increased risk for late recurrence. One reason might be disseminated tumor cells (DTCs), which split off in the early stages of the disease and metastasize into the bone marrow (BM).

Methods: We developed a novel multi-parameter immunofluorescence staining protocol using releasable and bleachable antibody-fluorochrome-conjugates. This sequential procedure enabled us to analyze six distinct phenotypical and therapy-related markers on the same DTC. We characterized BM aspirates from 29 patients with a HR+ tumor and a known positive DTC status-based on the standardized detection of epithelial cells in BM.

Results: Using the immunofluorescence staining, a total of 153 DTCs were detected. Luminal A patients revealed a higher DTC count compared with luminal B. The majority of the detected DTCs were CK-positive (128/153). However, in 16 of 17 luminal A patients we found HER2-positive DTCs. We detected CK-negative DTCs (25/153) in 12 of 29 patients. Of those cells, 76% were Ki67-positive and 68% were HER2-positive. Moreover, we detected DTC clusters consisting of mixed characteristics in 6 of 29 patients.

Conclusions: Using sequential multi-parameter imaging made it possible to identify distinct DTC profiles not solely based on epithelial features. Our findings indicate that characterization rather than quantification of DTCs might be relevant for treatment decisions.

Keywords: HER2; bone marrow; breast cancer; disseminated tumor cells; dormancy; hormone receptor; proliferation.

Grants and funding

This research was funded by internal means and received no external funding. The publication was funded by the Open Access Publishing Fund of Leipzig University, supported by the German Research Foundation within the program Open Access Publication Funding.