Abstract
The detection of circulating tumor cells (CTC) in breast cancer is strongly associated with disease relapse. Since it is unclear whether all CTCs are capable of generating metastasis, we investigated their apoptotic and proliferative status in 56 CTC-positive (29 early and 27 metastatic) patients with breast cancer. Double-staining immunofluorescence experiments were carried out in peripheral blood mononuclear cells (PBMC) cytospins, using the pancytokeratin A45-B/B3 antibody and either M30 (apoptotic marker) or Ki67 (proliferation marker) antibodies. Apoptosis was also evaluated using a polycaspase detection kit. Patients with metastatic disease had significantly lower numbers of apoptotic CTCs compared with patients with early breast cancer (polycaspase kit: 8.1% vs. 47.4% of the total CTC number; P = 0.0001; M30-antibody: 32.1% vs. 76.63%; P = 0.002). The median percentage of apoptotic CTCs per patient was also lower in patients with advanced compared with those with early disease (polycaspase kit: 0% vs. 53.6%; M30-antibody: 15% vs. 80%). Ki67-positive CTCs were identified in 51.7% and 44% of patients with early and metastatic disease, respectively. Adjuvant chemotherapy reduced both the number of CTCs per patient and the number of proliferating CTCs (63.9% vs. 30%). In conclusion, apoptotic CTCs could be detected in patients with breast cancer irrespective of their clinical status, though the incidence of detection is higher in early compared with metastatic patients. The detection of CTCs that survive despite adjuvant therapy implies that CTC elimination should be attempted using agents targeting their distinctive molecular characteristics.
Highlights
Circulating tumor cells (CTC) are increasingly considered as a "liquid biopsy" that allows the assessment of tumor changes over time by repeated blood draws [1]
We have reported that activated kinases such as phosphoAKT and phospho-PI3K that are involved in survival pathways are expressed in CTCs from patients with early and metastatic breast cancer [19, 20]
We have recently reported that activated kinases, participating in cell survival and proliferation such as AKT and PI3K are expressed in CTCs of patients with early and metastatic breast cancer [20]
Summary
Circulating tumor cells (CTC) are increasingly considered as a "liquid biopsy" that allows the assessment of tumor changes over time by repeated blood draws [1]. The presence of CTCs in the blood of patients with breast cancer has emerged as a poor prognostic indicator [2,3,4]. Metastasis is associated with the presence of disseminated (DTC) or circulating (CTC) tumor cells in the bone marrow and peripheral blood, respectively [5, 6]. Many CTCs migrate early from the primary tumor into the circulation, 97% of them will be cleared within a few days [6].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
