Title:
Circulating Cells in Cancer Detection

Contact:

Mukesh Verma, Ph.D.
Division of Cancer Prevention
National Cancer Institute
Executive Plaza North, EPN 3144
Bethesda, MD 20892
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 496-3893
FAX: (301) 402-8990
Email: vermam@mail.nih.gov

Objective of Project:

The objectives of this initiative are to develop novel technologies for capturing, enriching, and preserving exfoliated, abnormal cells and circulating DNA in body fluids or effusions and to develop methods for concentrating the enriched cells for biomarker studies. In body fluids, such as sputum, the number of exfoliated tumor cells is often small compared to the number of non-neoplastic cells. Therefore, the detection of exfoliated abnormal cells by routine cytopathology is often limited because few atypical cells may be present in the specimen. Thus, the development of enrichment methods is a prerequisite for the routine detection of small numbers of exfoliated cells and small amounts of subcellular materials in biological fluids for molecular analysis.

Description of Project:

The most common human tumors arise from epithelial surfaces (e.g., colon, lung, prostate, oral cavity, esophagus, stomach, uterine cervix, and bladder). Their development often becomes apparent when tumor cells exfoliate spontaneously into sputum, urine, or even into various effusions. The molecular and genetic abnormalities within these exfoliated cells could be used to detect and identify precancerous lesions or very early stage cancer if highly sensitive technologies were clinically available to identify the few abnormal cells among millions of normal cells. Abnormal exfoliated cells can be routinely identified by cytologic examination of brushings and fluids, from bronchi, pancreatic ducts, voided urine, and effusions. Currently fluids are usually processed by centrifugation or membrane filtration. However, the detection of abnormal exfoliated cells (for instance cancer cells) by routine cytopathological examination may be limited because the number of abnormal cells may be very small compared to the number of normal cells. Circulating DNA has also been used for cancer detection. New PCR-based technologies may substantially enhance the sensitivity, but current technologies for isolating exfoliated cells are too cumbersome to be of practical utility. Finding molecular and genetic biomarkers of early cancer represents an extraordinary opportunity for the National Cancer Institute (NCI) and is particularly important in detecting the emergence of precancerous cell populations.