Fluid phase of solid tumors, circulating tumor cells in high definition

Abstract

Abstract We have established a fluid phase biopsy approach that identifies circulating tumor cells (CTCs) in the context of peripheral blood leukocytes, with no protein-based enrichment, and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. We refer to this technique as the HD-CTC assay and report on the use of this methodology to characterize the incidence of HD-CTCs in peripheral blood samples from a small cohort of metastatic cancer patients, including those with prostate cancer, breast cancer, pancreatic cancer, along with set of normal controls. Importantly, we find HD-CTC clusters ranging from 2 HD-CTCs to greater than 30 HD-CTCs in the majority of the cancer patients in this cohort. As a case study, one patient was followed over time and both cytology from a solid tumor metastasis and the HD-CTCs were quantitatively characterized. This initial validation of an enrichment-free assay demonstrates the ability to identify significant numbers of HD-CTCs in a majority of patients in prostate, breast and pancreatic cancers. Due to the enrichment free approach, the HD-CTC assay has significant implications for determining the biology of cancer spread and therapy response in both the HD-CTC population and the populations of rare events that are outside of the strict HD-CTC definition but are still fully characterized and tracked in this assay. This fluid biopsy can then be used for routine pathology evaluation and additional molecular characterization. Future studies will investigate the clinical utility of this methodology.