Molecular detection of circulating tumor cells and cell-free nucleic acids

One of the key roles performed by pathologists is determination of the presence or absence of tumor in clinical samples. This is the basis for most approaches to staging, monitoring response to treatment, and detecting relapse of neoplasia and, as such, is a critical step in determining the course of patient management. Pathologists have utilized a variety of methods, continually seeking to improve assay performance and thus patient outcome. The literature reflects this quest, including reports assessing the increased sensitivity afforded by immunohistochemistry (IHC), flow cytometry, and, more recently, molecular approaches for the detection of tumor cells and nucleic acids in blood and bone marrow samples. The goal is, of course, the more accurate detection of disease spread and, ultimately, better patient care.This chapter addresses some of the recent work in tumor detection, focusing on molecular and, to some degree, immunofluorescent approaches for the detection of circulating tumor cells and free nucleic acids in clinical samples. A synopsis of the hundreds of articles published to date is beyond the scope of this chapter; instead, more general issues and findings are addressed, along with presentation of selected work. Several reviews are available for more detailed reading (Alix-Panabières and Pantel, Clin Chem 59:110-118, 2013; Pinzani et al., Methods 50:302-307, 2010; Pratt et al. Chem Eng Sci 66:1508-1522, 2011; Schwarzenbach et al., Nat Rev Clin Oncol 11:145-156, 2014).