Abstract and Introduction
Abstract
As the presence of tumor cells circulating in the blood is associated with systemic disease and shortened survival, the establishment of a method to detect circulating tumor cells (CTCs) is of critical importance for a more concise staging and follow-up of cancer patients. Recently, the most robust strategies for the determination of CTCs are the PCR-based methods and the CellSearch® system that exploits the immunofluorescent characterization and isolation of cancer cells. Herein, we analyzed the experimental strategies used for determining CTCs with respect to accuracy, sensitivity and reproducibility in cancers of the breast, colon, prostate and melanoma.
Introduction
The major cause of cancer-related death in patients with solid tumors is the presence of metastatic disease. The existence of malignant cells of epithelial origin in the blood – circulating tumor cells (CTCs) – has been known for over a century and has been associated with metastasis. It has been suggested that the hallmark of the 'invasive behavior' of a proportion of cancer cells is associated with escaping from the primary tumor mass and colonizing new terrain in the body where, at least initially, nutrients and space are not limited, and there form metastases.
Although there is a large number of different methods developed for determining DNA or protein concentrations in the blood or plasma of cancer patients and genetic or epigenetic alterations specific to tumors, all aiming at different biomarkers such as circulating nucleic acids and proteins with various techniques, recent evidence suggesting that the major cause of metastasis is the presence of CTCs in cancer patients holds tremendous promise for the identification of the potential for metastatic disease at very early stages, managing risk stratification in the adjuvant setting, monitoring responses to treatment, assessing disease recurrence and the prospective development of more effective and better tailored anticancer therapies for individual patients.
The rationale for measuring CTCs for disease that is not clinically or radiographically identifiable could be a major challenge for oncologists, as the cancer patient treatment arena is becoming congested with numerous types of therapies relative to specific clinicopathological parameters. Over the past few years, different approaches have been developed, prior to the detection of CTCs in different tumors. Each of these approaches has distinct advantages and disadvantages, with the most notable being sensitivity and specificity. Our aim is to critically analyze the major methodologies involved in the detection of CTCs, namely the CellSearch® system (Veridex, NJ, USA) and the PCR-based methods, and to discuss the advantages and drawbacks concerning the requirements of high sensitivity, high specificity and affordability.