Researchers have identified a novel signature of circulating tumor cells (CTCs) from breast cancer that metastasize to the brain and that may not be detected by the method of identification cleared by the FDA.

The FDA-approved CellSearch platform is based on the detection of antibodies that target the epithelial cell adhesion molecule (EpCAM), according to a statement from Baylor College of Medicine in Houston, Texas. But the biomarkers identified by Dario Marchetti, who is a pathologist at Baylor, and colleagues are present in CTCs that are EpCAM-negative, and as such, would not be detected by CellSearch.

The four brain metastasis selected markers (BMSMs) identified by Marchetti’s team are human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), heparanase (HPSE), and Notch1. These four proteins were already known to be associated with cancer metastasis. Now, this pattern of proteins has been found to spell out the signature of CTCs that metastasize to the brain.


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“CTC lines expressing the BMSM signature were highly invasive and capable of generating brain and lung metastases when xenografted [in mice],” affirmed Marchetti’s group in Science Translational Medicine (2013;5[180]:180ra48). “The presence of proteins of the BMSM CTC signature was also detected in the metastatic lesions of animals.”

Identifying and understanding the characteristics of CTCs are initial steps in developing new treatments for metastatic disease. Marchetti noted in the Baylor statement that he and his fellow investigators are not claiming that these biomarkers are the only important ones; the investigators are continuing to search for novel markers in brain metastasis that will make diagnosis and monitoring even more targeted.