Abstract
IntroductionThe origin and clinical relevance of circulating cell-free tumor DNA in the blood of cancer patients is still unclear. Here we investigated whether the detection of this DNA is related to bone marrow (BM) micrometastasis and tumor recurrence in breast cancer patients.MethodsBM aspirates of 81 primary breast cancer patients were analyzed for the presence of disseminated tumor cells (DTC) by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. PCR-based fluorescence microsatellite analysis was performed for detection of loss of heterozygosity (LOH) at 6 polymorphic markers using cell-free serum DNA. The data were correlated with established risk factors, and patients were followed-up over 6-10 years.ResultsLOH was detected in 33.5% of blood samples. The occurrence of LOH at the entire microsatellite marker set correlated with histopathology (P = 0.05) and grading (P = 0.006) of the primary tumor. The genomic region characterized by marker D9S171 was only affected by LOH in patients with increased tumor stages (pT2-4, P < 0.05) and older age (≥ 55 years, P = 0.05). Kaplan-Meier analysis showed that LOH at D3S1255 (P = 0.009) and D9S171 (P = 0.001) were significantly associated with tumor relapse. In BM, DTC were detected in 39.5% of the patients, and this finding correlated with distant metastases (P < 0.05). Patients with DTC-positive BM had higher DNA yields in their blood than patients with DTC-negative BM (P < 0.05). However, no significant correlations were found between the presence of DTC in BM and the detection of marker-specific LOH on blood DNA.ConclusionsThe detection of LOH on cell-free tumor DNA in blood is unrelated to BM micrometastasis and provides independent information on breast cancer progression.
Highlights
The origin and clinical relevance of circulating cellfree tumor DNA in the blood of cancer patients is still unclear
In bone marrow (BM), disseminated tumor cells (DTC) were detected in 39.5% of the patients, and this finding correlated with distant metastases (P < 0.05)
The detection of loss of heterozygosity (LOH) on cell-free tumor DNA in blood is unrelated to BM micrometastasis and provides independent information on breast cancer progression
Summary
The origin and clinical relevance of circulating cellfree tumor DNA in the blood of cancer patients is still unclear. Hematogenous dissemination of tumor cells is a common phenomenon in breast cancer, which escapes detection by common staging procedures and limits the improvement of breast cancer mortality rates In this regard, the spread of disseminated tumor cells (DTC) into the bone marrow (BM) is recorded in up to 40% of breast cancer patients at primary diagnosis, and their presence is being considered as an independent prognostic factor for reduced survival, as demonstrated by a pooled analysis of more than 4700 breast cancer patients [1]. Our recent study on cell-free DNA in blood from prostate cancer patients suggested that this DNA may be originate from micrometastatic lesions [12] This finding provided the rationale for the current study, which evaluates whether the detection of tumor-specific DNA in the blood of breast cancer patients is related to the presence of BM micrometastasis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
