Journal of the National Cancer Institute Advance Access originally published online on December 30, 2008
JNCI Journal of the National Cancer Institute 2009 101(1):61-66; doi:10.1093/jnci/djn419
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BRIEF COMMUNICATION |
Anti-Epithelial Cell Adhesion Molecule Antibodies and the Detection of Circulating Normal-Like Breast Tumor Cells
Affiliations of authors: Department of Medical Oncology, Josephine Nefkens Institute and Cancer Genomics Centre (AMS, JB, JWMM, JAF), Department of Medical Oncology, Daniel den Hoed Cancer Center (JK, PvdS, J-WG, SS), and Department of Medical Oncology, Josephine Nefkens Institute (FE, MS), Erasmus MC, Rotterdam, the Netherlands
Correspondence to: Anieta M. Sieuwerts, PhD, Department of Medical Oncology, Josephine Nefkens Institute, Erasmus MC, Rm BE-400, Dr Molewaterplein 50, 3015 GE Rotterdam, the Netherlands (e-mail: a.sieuwerts{at}erasmusmc.nl).
Identification of specific subtypes of circulating tumor cells in peripheral blood of cancer patients can provide information about the biology of metastasis and improve patient management. However, to be effective, the method used to identify circulating tumor cells must detect all tumor cell types. We investigated whether the five subtypes of human breast cancer cells that have been defined by global gene expression profiling—normal-like, basal, HER2-positive, and luminal A and B—were identified by CellSearch, a US Food and Drug Administration–approved test that uses antibodies against the cell surface–expressed epithelial cell adhesion molecule (EpCAM) to isolate circulating tumor cells. We used global gene expression profiling to determine the subtypes of a well-defined panel of 34 human breast cancer cell lines (15 luminal, nine normal-like, five basal-like, and five Her2-positive). We mixed 50-150 cells from 10 of these cell lines with 7.5 mL of blood from a single healthy human donor, and the mixtures were subjected to the CellSearch test to isolate the breast cancer cells. We found that the CellSearch isolation method, which uses EpCAM on the surface of circulating tumor cells for cell isolation, did not recognize, in particular, normal-like breast cancer cells, which in general have aggressive features. New tests that include antibodies that specifically recognize normal-like breast tumor cells but not cells of hematopoietic origin are needed.
| Context and Caveats Prior knowledge Identification of specific subtypes of circulating tumor cells in the peripheral blood of cancer patients can provide important prognostic information, but to be effective, the method used must recognize all tumor cell types. Study design The subtype of 19 well-characterized breast cancer cell lines was obtained by use of gene expression profiling, including normal-like, basal-like, HER2-positive, and luminal A and B. Cells from each line were mixed with blood from a healthy donor and subjected to the CellSearch circulating tumor cell assay. Contribution The CellSearch assay, which uses epithelial cell adhesion molecules on the cell surface, did not recognize normal-like breast cancer cells, although other subtypes were recognized. Implications Normal-like breast cancer cells have especially aggressive features, and so assays that recognize this subtype would provide valuable prognostic information. New assays are needed that include antibodies that specifically recognize this breast cancer subtype but not other cell types, including those of hematopoietic origin. Limitations Only homogeneous breast cancer cell lines with known subtypes were investigated. From the Editors
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Manuscript received June 12, 2008; revised October 7, 2008; accepted October 20, 2008.
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J Natl Cancer Inst 2009 101: 1.
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