Bone Marrow Aspiration for Disseminated Tumor Cell Detection: A Must-Have Test or Is the Jury Still Out?

2009 ◽  
Vol 27 (10) ◽  
pp. 1531-1533 ◽  
Author(s):  
Howard I. Scher ◽  
Klaus Pantel
Keyword(s):  
Bone Marrow ◽  
Tumor Cell ◽  
Bone Marrow Aspiration ◽  
Cell Detection ◽  
Tumor Cell Detection

In Vivo Cytoreduction Studies and Cell Sorting–Enhanced Tumor-Cell Detection in High-Risk Neuroblastoma Patients: Implications for Leukapheresis Strategies

2000 ◽  
Vol 18 (22) ◽  
pp. 3829-3836 ◽  
Author(s):  
Lawrence B. Faulkner ◽  
Alberto Garaventa ◽  
Antonella Paoli ◽  
Veronica Tintori ◽  
Angela Tamburini ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Tumor Cell ◽  
Bone Marrow Involvement ◽  
Cell Detection ◽  
Hematopoietic Stem ◽  
Tumor Cell Detection ◽  
Bone Marrow Disease ◽  
Immunomagnetic Enrichment

PURPOSE: To improve autologous leukapheresis strategies in high-risk neuroblastoma (NB) patients with extensive bone marrow involvement at diagnosis. PATIENTS AND METHODS: Anti-GD2 immunocytochemistry (sensitivity, 1 in 105 to 106 leukocytes) was used to evaluate blood and bone marrow disease at diagnosis and during the recovery phase of the first six chemotherapy cycles in 57 patients with stage 4 NB and bone marrow disease at diagnosis. A total of 42 leukapheresis samples from the same patients were evaluated with immunocytology, and in 24 of these patients, an anti-GD2 immunomagnetic enrichment step was used to enhance tumor-cell detection. RESULTS: Tumor cytoreduction was much faster in blood compared with bone marrow (3.2 logs after the first cycle and 2.1 logs after the first two cycles, respectively). Bone marrow disease was often detectable throughout induction, with a trend to plateau after the fourth cycle. By direct anti-GD2 immunocytology, a positive leukapheresis sample was obtained in 7% of patients after either the fifth or sixth cycle; when NB cell immunomagnetic enrichment was applied, 25% of patients had a positive leukapheresis sample (sensitivity, 1 in 107 to 108 leukocytes). CONCLUSION: Standard chemotherapy seems to deliver most of its in vivo purging effect within the first four cycles. In patients with overt marrow disease at diagnosis, postponing hematopoietic stem-cell collection beyond this point may not be justified. Tumor-cell clearance in blood seems to be quite rapid, and earlier collections via peripheral-blood leukapheresis might be feasible. Immunomagnetically enhanced NB cell detection can be highly sensitive and can indicate whether ex vivo purging should be considered.

Expression of MUC-1 Epitopes on Normal Bone Marrow: Implications for the Detection of Micrometastatic Tumor Cells

1999 ◽  
Vol 17 (5) ◽  
pp. 1535-1535 ◽  
Author(s):  
Wolfram Brugger ◽  
Hans-Jörg Bühring ◽  
Frank Grünebach ◽  
Wichard Vogel ◽  
Sepp Kaul ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Cell ◽  
Western Blotting ◽  
Mononuclear Cells ◽  
Cell Detection ◽  
Tumor Cell Detection ◽  
Peripheral Blood Progenitor Cells ◽  
Normal Human ◽  
Positive Results

PURPOSE: The expression of the carcinoma-associated mucin MUC-1 is thought to be restricted to epithelial cells and is used for micrometastatic tumor cell detection in patients with solid tumors, including those with breast cancer. Little is known, however, about the expression of MUC-1 epitopes in normal hematopoietic cells. MATERIALS AND METHODS: MUC-1 expression was analyzed by flow cytometry and immunocytology on bone marrow (BM) mononuclear cells and purified CD34+ cells from healthy volunteers, using different anti-MUC-1–specific monoclonal antibodies. In addition, Western blotting of MUC-1 proteins was performed. RESULTS: Surprisingly, 2% to 10% of normal human BM mononuclear cells expressed MUC-1, as defined by the anti–MUC-1 antibodies BM-2 (2E11), BM-7, 12H12, MAM-6, and HMFG-1. In contrast, two antibodies recognizing the BM-8 and the HMFG-2 epitopes of MUC-1 were not detected. MUC-1+ cells from normal BM consisted primarily of erythroblasts and normoblasts. In agreement with this, normal CD34+ cells cultured in vitro to differentiate into the erythroid lineage showed a strong MUC-1 expression on day 7 proerythroblasts. Western blotting of these cells confirmed that the reactive species is the known high molecular weight MUC-1 protein. CONCLUSION: Our data demonstrate that some MUC-1 epitopes are expressed on normal BM cells and particularly on cells of the erythroid lineage. Hence the application of anti–MUC-1 antibodies for disseminated tumor cell detection in BM or peripheral blood progenitor cells may provide false-positive results, and only carefully evaluated anti–MUC-1 antibodies (eg, HMFG-2) might be selected. Furthermore, MUC-1–targeted immunotherapy in cancer patients might be hampered by the suppression of erythropoiesis.

Low tumor cell detection rate in bone marrow of patients with primary breast cancer after elimination of stroma cells: Comparison of immunocytology and molecular analysis of CK19 and mammaglobin 1

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1075-1075
Author(s):  
S. Kaul ◽  
M. Aggarwal ◽  
A. Eichler ◽  
C. Sohn ◽  
N. Fersis
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Primary Breast Cancer ◽  
Detection Rate ◽  
Cell Detection ◽  
Breast Cancer Patients ◽  
Rt Pcr ◽  
Tumor Cell Detection

1075 Background: Rapidly self-renewing stroma cells of the bone marrow (RS cells) are MUC-1 and cytokeratin positive at a rate of 56% (475/850). Elimination of RS cells by size exclusion results in a positivity rate of 2.6% (36/1407) in primary breast cancer patients. We have used preanalytical immunomagnetic tumor cell enrichment followed by molecular detection of CK19 and Mammaglobin1 (MA) transcripts for an independent verification of the bright-field immunocytology results. Material and Methods: Mononuclear cells (2x106) from bone marrow of 1,407 patients with primary breast cancer were analysed by standardized cytospin immunocytology techniques. Disseminated tumor cells (DTC) were stained with CK8/18/19 antibodies 5D3 and A45-B/B3 using either the APAAP technique (Dako Techmate 500) or the enhanced SA-FastRed method (Ventana). Parallel DTC consisted of immunomagnetic tumor cell selection of 1x107 BM cells using the cell membrane glycoproteins EpCAM and MUC-1 as targets. CK 19 and MA transcripts were determined by conventional and quantitative real time RT-PCR. Results: Using acetic acid and periodate blocking steps before immunocytology 36 from 1407 (2.6%) breast cancer patients operated between 1999 and 2005 at the University Hspital Heidelberg were scored DCT positive using computer assisted automated (Chromavision ACIS II) picture analysis. From this group 186 bone marrow samples were used for molecular tumor cell detection. By RT-PCR analysis of 1x107 immunomagnetically purified BM cells only 6 from 186 (3.2%) samples were CK19 and MG positive. Discussion: Detection rates of tumor cells in bone marrow from non-metastatic breast cancer patients has been reported to be in the range of 0% to 100%. We show here that proliferating bone marrow stroma cells of the RS type are positive for various antigens including CK polypeptides 7, 8, 18 and 19. Elimination of these cells by size exclusion results in a tumor cell detection rate of 2,6% in 1,407 BM probes. This low detection rate could be verified in 186 BM probes by CK19 and mammaglobin1 RT-PCR. We conclude that standard immunocytology in bone marrow is severely impaired by cytokeratin expression of RS-type stroma cells. No significant financial relationships to disclose.

Detection of tumor cells in bone marrow of patients with primary breast cancer: a prognostic factor for distant metastasis.

1992 ◽  
Vol 10 (10) ◽  
pp. 1534-1539 ◽  
Author(s):  
I J Diel ◽  
M Kaufmann ◽  
R Goerner ◽  
S D Costa ◽  
S Kaul ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Distant Metastasis ◽  
Primary Breast Cancer ◽  
Nodal Status ◽  
Cell Detection ◽  
Tumor Cell Detection ◽  
Human Breast Carcinomas

PURPOSE At the time of primary surgery, approximately 90% of all patients with breast cancer are free of metastases, but in the next 5 years almost 50% of them will relapse. We evaluated the significance of the presence of tumor cells in bone marrow of patients with primary breast cancer to investigate their predictive value for relapse. PATIENTS AND METHODS Two hundred sixty patients with primary breast cancer were examined for tumor cells in bone marrow aspirates taken from six sites of the skeleton. After density centrifugation, cells in interphase were smeared and stained. For the immunocytologic reaction, we used a new monoclonal antibody (2E11) that was reactive with the core protein of the tumor-associated glycoprotein TAG12. TAG12 is secreted by nearly all human breast carcinomas. RESULTS A significant correlation was found between tumor-cell detection and tumor stage (P < .0001), nodal status (P < .0001), and tumor grading (P = .002). A good relation to progesterone receptor (PR; P = .008) was found, but there was no correlation to estrogen receptor (ER) and menopausal status. Follow-up examinations showed distant metastases in 26 of 211 patients (15%). Twenty-two relapses occurred among the 81 patients with 2E11-positive cells in bone marrow, but only four occurred among the 130 patients without tumor-cell detection. CONCLUSIONS This study suggests that tumor-cell detection in bone marrow of patients with primary breast carcinoma is a good predictor for all distant relapses (P < .0005, Cox multiple regression analysis) and provides additional information in regard to other prognostic factors. The highest predicting value for distant metastasis results from the combination of nodal status, negative PR, and tumor-cell presence in bone marrow.

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