Circulating tumor cells (CTCs) have been of interest to the medical and research communities for over a century (1). These cells represent an important link to the process of metastasis, and investigators have been interested in using these cells to establish the diagnosis and prognosis of cancer. In addition, these cells are a potential source of biological information that can be used to predict responsiveness to various treatment agents, monitor response to therapy, and provide tissue for further research into the mechanisms of malignant transformation and resistance. CTCs have been documented in multiple epithelial tumor types (2), but the largest body of data comes from studies of women with breast cancer.
Historically, CTC research has been limited by issues of sensitivity, specificity, and reproducibility. These limitations are primarily due to the rarity of CTCs, which occur at a frequency of one tumor cell per 1 x 105-7 peripheral blood mononuclear cells (3). In the 1950s and 1960s, there was great excitement surrounding the investigation of CTCs (4). However, the methodologies of the time relied almost exclusively on the microscopic properties of morphology and size as well as the physical property of density. It soon became apparent that these physical criteria alone were not sufficient for the identification of CTCs. Many of the cells identified during this era were believed to have been false positive cells that result from artifacts of sample preparation and from misclassification of immature leukocytes (5). Thus, morphological characteristics alone did not provide adequate specificity, and no further meaningful progress was made in the field of CTC research until the advent of antibody and nucleic acid technologies, which allowed the identification of biological characteristics of these cells.
Was this article helpful?