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 services)
Telephone: (301) 496-3893
FAX: (301) 402-8990
Email: vermam@mail.nih.gov

Objective of Project:

The objective of this project is to support the development of novel technologies for capturing, enriching, and preserving exfoliated abnormal cells in body fluids or effusions as well as of methods for concentrating the enriched cells for use in 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. As a result, the detection of exfoliated abnormal cells by routine cytopathology is often limited because few atypical cells may be present in a given specimen. Therefore, the development of enrichment methods is a prerequisite for the routine detection (by molecular analysis or other methods) of small numbers of exfoliated cells and small amounts of subcellular materials in biological fluids.

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 cancers 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 examinations 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 example, cancer cells) in specimens from patients by routine cytopathological examination may be limited because the numbers of abnormal cells may be very small compared to the numbers of normal cells. 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.