Characterization of Disseminated Tumor Cells (DTCs) in Patients with Triple-Negative Breast Cancer (TNBC)
Triple negative breast cancer (TNBC) is the most aggressive molecular subtype and it lacks targetable receptors. Patients have an increased risk of recurrence and poor prognosis. Little is known concerning the characteristics of disseminated tumor cells (DTCs) and their role in TNBC patients. We ana...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/14/12/857 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850156253631741952 |
|---|---|
| author | Anne Eckardt Ivonne Nel Laura Weydandt Elisa Brochwitz Anne Kathrin Höhn Karsten Winter Bahriye Aktas |
| author_facet | Anne Eckardt Ivonne Nel Laura Weydandt Elisa Brochwitz Anne Kathrin Höhn Karsten Winter Bahriye Aktas |
| author_sort | Anne Eckardt |
| collection | DOAJ |
| description | Triple negative breast cancer (TNBC) is the most aggressive molecular subtype and it lacks targetable receptors. Patients have an increased risk of recurrence and poor prognosis. Little is known concerning the characteristics of disseminated tumor cells (DTCs) and their role in TNBC patients. We analyzed the bone marrow aspirates of 80 patients with primary (<i>n</i> = 67) or recurrent (<i>n</i> = 13) TNBC, using a multi-parameter immunofluorescence staining procedure, including Pan-CK as an epithelial marker, vimentin (vim) as a marker of epithelial–mesenchymal transition, Ki67 for cell proliferation, and HER2 as well as PD-L1 as therapy-related markers. The DTC positive rate was 56% (<i>n</i>= 45) among the cohort. We found 20 different DTC subpopulations. The most frequently detected profile was CK+Vim+Ki67+ (<i>n</i> = 75 cells). The occurrence of CK- DTCs (<i>n</i> = 69) was significantly correlated to PD-L1 (r = −0.305, <i>p</i> < 0.01) and HER2 positivity (r = −0.234, <i>p</i> < 0.001). DTC positive patients that received neoadjuvant chemotherapy (NACT) and did not reach pathologic complete response were more likely to have CK- DTCs. Our data indicate that the occurrence of DTC subpopulations positive for Vim, Ki67, and HER2 appear to be markers for bad prognosis and could be therapeutically relevant. Furthermore, our results raise the question of whether DTCs are dormant in TNBC patients and persistent towards chemotherapy. |
| format | Article |
| id | doaj-art-a95b1261d9ff4dd19e3ea97bb060d9c8 |
| institution | OA Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-a95b1261d9ff4dd19e3ea97bb060d9c82025-08-20T02:24:37ZengMDPI AGCells2073-44092025-06-01141285710.3390/cells14120857Characterization of Disseminated Tumor Cells (DTCs) in Patients with Triple-Negative Breast Cancer (TNBC)Anne Eckardt0Ivonne Nel1Laura Weydandt2Elisa Brochwitz3Anne Kathrin Höhn4Karsten Winter5Bahriye Aktas6Department of Gynecology, Medical Center, Leipzig University, 04103 Leipzig, GermanyDepartment of Gynecology, Medical Center, Leipzig University, 04103 Leipzig, GermanyDepartment of Gynecology, Medical Center, Leipzig University, 04103 Leipzig, GermanyDepartment of Gynecology, Medical Center, Leipzig University, 04103 Leipzig, GermanyDepartment of Pathology, Medical Center, Leipzig University, 04103 Leipzig, GermanyInstitute of Anatomy, Medical Faculty, Leipzig University, 04103 Leipzig, GermanyDepartment of Gynecology, Medical Center, Leipzig University, 04103 Leipzig, GermanyTriple negative breast cancer (TNBC) is the most aggressive molecular subtype and it lacks targetable receptors. Patients have an increased risk of recurrence and poor prognosis. Little is known concerning the characteristics of disseminated tumor cells (DTCs) and their role in TNBC patients. We analyzed the bone marrow aspirates of 80 patients with primary (<i>n</i> = 67) or recurrent (<i>n</i> = 13) TNBC, using a multi-parameter immunofluorescence staining procedure, including Pan-CK as an epithelial marker, vimentin (vim) as a marker of epithelial–mesenchymal transition, Ki67 for cell proliferation, and HER2 as well as PD-L1 as therapy-related markers. The DTC positive rate was 56% (<i>n</i>= 45) among the cohort. We found 20 different DTC subpopulations. The most frequently detected profile was CK+Vim+Ki67+ (<i>n</i> = 75 cells). The occurrence of CK- DTCs (<i>n</i> = 69) was significantly correlated to PD-L1 (r = −0.305, <i>p</i> < 0.01) and HER2 positivity (r = −0.234, <i>p</i> < 0.001). DTC positive patients that received neoadjuvant chemotherapy (NACT) and did not reach pathologic complete response were more likely to have CK- DTCs. Our data indicate that the occurrence of DTC subpopulations positive for Vim, Ki67, and HER2 appear to be markers for bad prognosis and could be therapeutically relevant. Furthermore, our results raise the question of whether DTCs are dormant in TNBC patients and persistent towards chemotherapy.https://www.mdpi.com/2073-4409/14/12/857triple negativebreast cancer (TNBC)disseminated tumor cells (DTCs)bone marrowneoadjuvant chemotherapypathologic complete remission (pCR) |
| spellingShingle | Anne Eckardt Ivonne Nel Laura Weydandt Elisa Brochwitz Anne Kathrin Höhn Karsten Winter Bahriye Aktas Characterization of Disseminated Tumor Cells (DTCs) in Patients with Triple-Negative Breast Cancer (TNBC) Cells triple negative breast cancer (TNBC) disseminated tumor cells (DTCs) bone marrow neoadjuvant chemotherapy pathologic complete remission (pCR) |
| title | Characterization of Disseminated Tumor Cells (DTCs) in Patients with Triple-Negative Breast Cancer (TNBC) |
| title_full | Characterization of Disseminated Tumor Cells (DTCs) in Patients with Triple-Negative Breast Cancer (TNBC) |
| title_fullStr | Characterization of Disseminated Tumor Cells (DTCs) in Patients with Triple-Negative Breast Cancer (TNBC) |
| title_full_unstemmed | Characterization of Disseminated Tumor Cells (DTCs) in Patients with Triple-Negative Breast Cancer (TNBC) |
| title_short | Characterization of Disseminated Tumor Cells (DTCs) in Patients with Triple-Negative Breast Cancer (TNBC) |
| title_sort | characterization of disseminated tumor cells dtcs in patients with triple negative breast cancer tnbc |
| topic | triple negative breast cancer (TNBC) disseminated tumor cells (DTCs) bone marrow neoadjuvant chemotherapy pathologic complete remission (pCR) |
| url | https://www.mdpi.com/2073-4409/14/12/857 |
| work_keys_str_mv | AT anneeckardt characterizationofdisseminatedtumorcellsdtcsinpatientswithtriplenegativebreastcancertnbc AT ivonnenel characterizationofdisseminatedtumorcellsdtcsinpatientswithtriplenegativebreastcancertnbc AT lauraweydandt characterizationofdisseminatedtumorcellsdtcsinpatientswithtriplenegativebreastcancertnbc AT elisabrochwitz characterizationofdisseminatedtumorcellsdtcsinpatientswithtriplenegativebreastcancertnbc AT annekathrinhohn characterizationofdisseminatedtumorcellsdtcsinpatientswithtriplenegativebreastcancertnbc AT karstenwinter characterizationofdisseminatedtumorcellsdtcsinpatientswithtriplenegativebreastcancertnbc AT bahriyeaktas characterizationofdisseminatedtumorcellsdtcsinpatientswithtriplenegativebreastcancertnbc |