Anti-Epithelial Cell Adhesion Molecule Antibodies and the Detection of Circulating Normal-Like Breast Tumor Cells

• Published in: JNCI : Journal of the National Cancer Institute Vol. 101; no. 1; pp. 61 - 66
• Main Authors: Sieuwerts, Anieta M., Kraan, Jaco, Bolt, Joan, van der Spoel, Petra, Elstrodt, Fons, Schutte, Mieke, Martens, John W. M., Gratama, Jan-Willem, Sleijfer, Stefan, Foekens, John A.
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 07.01.2009; Oxford Publishing Limited (England)
• Subjects: Antibodies, Neoplasm - blood; Antigens, Neoplasm - immunology; Biological and medical sciences; Biomarkers, Tumor - blood; Breast cancer; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Brief Communication; Cell adhesion & migration; Cell Adhesion Molecules - immunology; Cell Line, Tumor; Cellular biology; Epithelial Cell Adhesion Molecule; Female; Gene expression; Gene Expression Profiling; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Neoplastic Cells, Circulating - pathology; Predictive Value of Tests; Research Design; Tumors; Human; Mammary gland diseases; Breast disease; Cancerology; Antibody; Cell adhesion molecule; Epithelial cell; Breast cancer; Malignant tumor; Diagnosis; Cancer
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/djn419

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.