Comparative evaluation of cell-free tumor DNA in blood and disseminated tumor cells in bone marrow of patients with primary breast cancer.
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Comparative evaluation of cell-free tumor DNA in blood and disseminated tumor cells in bone marrow of patients with primary breast cancer. / Schwarzenbach, Heidi; Pantel, Klaus; Kemper, Birthe; Beeger, Cord; Otterbach, Friedrich; Kimmig, Rainer; Kasimir-Bauer, Sabine.
In: BREAST CANCER RES, Vol. 11, No. 5, 5, 2009, p. 71.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Comparative evaluation of cell-free tumor DNA in blood and disseminated tumor cells in bone marrow of patients with primary breast cancer.
AU - Schwarzenbach, Heidi
AU - Pantel, Klaus
AU - Kemper, Birthe
AU - Beeger, Cord
AU - Otterbach, Friedrich
AU - Kimmig, Rainer
AU - Kasimir-Bauer, Sabine
PY - 2009
Y1 - 2009
N2 - INTRODUCTION: The 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. METHODS: BM 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. RESULTS: LOH 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 (> or = 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. CONCLUSIONS: The detection of LOH on cell-free tumor DNA in blood is unrelated to BM micrometastasis and provides independent information on breast cancer progression.
AB - INTRODUCTION: The 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. METHODS: BM 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. RESULTS: LOH 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 (> or = 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. CONCLUSIONS: The detection of LOH on cell-free tumor DNA in blood is unrelated to BM micrometastasis and provides independent information on breast cancer progression.
U2 - 10.1186/bcr2404
DO - 10.1186/bcr2404
M3 - SCORING: Zeitschriftenaufsatz
VL - 11
SP - 71
JO - BREAST CANCER RES
JF - BREAST CANCER RES
SN - 1465-5411
IS - 5
M1 - 5
ER -