Circulating Tumor Cells (CTCs): Definition and Clinical Significance

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Circulating Tumor Cells (CTCs): Definition and Clinical Significance

Circulating tumor cells (CTCs) are cells that have detached from a primary tumor and circulate in the bloodstream. CTCs can be considered the seeds for the subsequent growth of additional tumors (metastases); therefore, CTCs are capable of metastasizing to other areas of the body and may create new tumors in different tissues or organs. Typically, an elevation in CTCs at any time during the clinical treatment of cancers is an indicator of cancer progression.
There are several types of CTCs that have variable characteristics and morphologies involving their nucleus, cell size, fragmentations and cytoplasmic characteristics, and cell clusters. These differences in cellular characteristics and morphology can be important in identifying the prognostic and therapeutic implications for the disease.
Clinically, when CTCs are present in the bloodstream, they exist in very small amounts. In patients with metastatic disease, CTCs are typically found in frequencies on the order of 1–10 CTC per mL of whole blood. It is estimated that among the cells that have detached from the primary tumor, only 0.01% can form metastases. Because of the low frequency of CTCs in the bloodstream, their detection can be difficult. This difficulty requires technologies and approaches for CTC identification capable of isolating 1 CTC per mL of blood and able to identify the various CTC types in sufficiently high definition and quantity to meet diagnostic criteria.
To date, CTCs have been detected in several cancers including breast, prostate, lung, and colon. A variety of methods have been developed to isolate and identify CTCs; however, at this time the only FDA-approved method for enumeration of CTCs in whole blood is the CELLSEARCH® system. Extensive clinical testing using this method has demonstrated that the presence of CTCs in the bloodstream is a strong prognostic factor for assessing overall survival in patients with metastatic breast, colorectal, or prostate cancer.