<unk> s that originate from carcinomas (cancers of epithelial origin, which are the most prevalent) can be classified according to the expression of epithelial markers, as well as their size and whether they are apoptotic. In general,<unk> s are anoikis-resistant, which means that they can survive in the bloodstream without attaching to a substrate. # Traditional<unk> s are characterised by an intact, viable nucleus; the expression of EpCAM and cytokeratins, which demonstrate epithelial origin; the absence of CD45, indicating the<unk>  is not of hematopoietic origin; and their larger size, irregular shape or subcellular morphology. # Cytokeratin-negative<unk> s are characterised by the lack of EpCAM or cytokeratins, which may indicate an undifferentiated phenotype<unk>  cancer stem<unk> s) or the acquisition of a mesenchymal phenotype (known as epithelial-mesenchymal transition or EMT). These populations of<unk> s may be the most resistant and most prone to metastasis. They are also more difficult to isolate because they express neither cytokeratins nor CD45. Otherwise, their morphology, gene expression and genomics are similar to those of other cancer<unk> s. # Apoptotic<unk> s are traditional<unk> s that are undergoing apoptosis (programmed<unk>  death). These may be used to monitor treatment response, as done experimentally by the Epic Sciences method, which identifies nuclear fragmentation or cytoplasmic blebbing associated with apoptosis. Measuring the ratio of traditional<unk>  to apoptotic<unk> s—from baseline to therapy—provides clues to treatment efficacy in targeting and killing cancer<unk> s. # Small<unk> s are cytokeratin-positive and CD45-negative, but with sizes and shapes similar to white blood<unk> s. Importantly, small<unk> s have cancer-specific biomarkers that identify them as<unk> s. Small<unk> s have been implicated in progressive disease and differentiation into small<unk>  carcinomas, which often require a different therapeutic course.<unk>  clusters<unk>  clusters are two or more individual<unk> s bound together. The<unk>  cluster may contain traditional, small or CK-<unk> s. These clusters have cancer-specific biomarkers that identify them as<unk> s. Several studies have reported that the presence of these clusters is associated with increased metastatic risk and poor prognosis. For example, one study involving prostate cancer showed an eight-fold longer mean survival rate for patients with only single<unk> s versus those with<unk>  clusters, while other studies have shown similar correlations for colon cancer. In addition, enumerating<unk>  clusters can provide useful prognostic information for patients with already elevated<unk>  levels. However, one study has reported that contrary to existing consensus, at least a discrete population of these clusters are non-malignant, and derive instead from the tumor endothelium. These<unk>  tumor-endothelial clusters also show epithelial-mesenchymal markers but do not mirror the genetics of the primary tumor. Previously it was assumed that<unk>  clusters could not pass through narrow vessels, such as capillaries, due to their overall size. However, it has been shown that<unk>  clusters can "unwind" through "selective cleavage of intercellular adhesions" to traverse these constrictions single-file, then reverse the process once clear. This behavior could be a factor in why<unk>  clusters have such a significant metastatic potential.
Circulating tumor cell
Circulating tumor DNA
Autologous patient-specific tumor antigen response
Pathogenic fungus
Focus of infection
Vaccine-induced seropositivity
Carcinogenic parasite
Tumor-homing bacteria