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Immunomagnetic Detection of Micrometastatic Cells in Bone Marrow of Colorectal Cancer Patients¹

Department of Tumor Biology, Institute for Cancer Research and The Norwegian Radium Hospital, 0310 Oslo, Norway [K. F., R. S. F., Ø. F.]; Department of Surgery and Institute for Surgical Research, The National Hospital, 0027 Oslo, Norway [K. B.]; Department of Surgery, Ullevål Hospital, 0450 Oslo, Norway [H. O. J.]; Department of Surgery, Akershus Central Hospital, 1474 Nordbyhagen, Norway [E. H.]; Department of Surgery, Bærum Hospital, 1346 Gjettum, Norway [R. R.]; Department of Surgery, Aker Hospital, Oslo, Norway [L. H.]; Diakonhjemmet Hospital, 0319 Oslo, Norway [J. H. S.]; and SINTEF Unimed, The Norwegian Centre for Health Technology Assessment, 0314 Oslo, Norway [O. S.]

Detection of micrometastatic cells in bone marrow (BM) may potentially be of prognostic value in colorectal cancer (CRC). In the present study, we have evaluated our immunomagnetic detection method in model experiments and on BM samples from CRC patients. In repeated experiments, 11 of 12 CRC cell lines consistently bound MOC31 antibody-coated magnetic particles with an average of 98% of the cells being rosetted with the beads. When different numbers of CRC cells (20, 100, 200, and 1000) were admixed to 1 x 10⁷ mononuclear cells (MNCs) from BM, a mean of 77% of the cancer cells was recovered. In BM samples obtained from CRC patients at primary surgery, rosetted tumor cells were detected in 46 of 275 samples (17%) upon screening of 2 x 10⁷ MNCs/sample. The fractions positive were: 10% (5 of 49) in Dukes’ A; 17% (20 of 115) in Dukes’ B; 23% (18 of 78) in Dukes’ C; and 9% (3 of 33) in Dukes’ D. Of 206 control samples, three (1.5%) contained cells in BM that formed rosettes with the MOC31 beads. In positive samples, a median of eight tumor cells (range, 2–120) were identified per 20-µl examined fraction, representing about one-tenth of the total sample. The results demonstrate the feasibility of using the immunomagnetic method for detection of micrometastatic CRC cells. Furthermore, that screening of 2 x 10⁷ MNCs in a BM sample can be completed in <3 h makes the method an attractive alternative to other techniques.

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