Circulating aberrant cells increase as non-small cell lung cancer progresses.
HOUSTON — A novel approach detects genetically abnormal cells in the
blood of non-small cell lung cancer patients that match abnormalities
found in tumor cells and increase in number with the severity of the
disease, a research team led by scientists at The
University of Texas MD Anderson Cancer Center report in the journal Clinical Cancer Research.
Lung cancer patients in the study also had many times the number of
these circulating abnormal cells than study volunteers in a closely
matched control group.
“We suspect additional research will show that these circulating
abnormal cells are circulating non-small cell lung cancer cells,” said
study corresponding author Ruth Katz, M.D., professor in MD Anderson’s Department of Pathology.
“Blood tests for these circulating tumor cells could be used to
diagnose lung cancer earlier, monitor response to therapy and detect
residual disease in patients after treatment.”
Katz and colleagues conducted what they believe to be the first
study to use a technique called fluorescence in situ hybridization
(FISH) to detect abnormal circulating cells that have aberrations found
in non-small cell lung cancer. FISH detects and quantifies abnormal
cells by using dye-labeled DNA probes of cell chromosomes that cause
cells with the targeted genetic abnormalities to light up when viewed
under a fluorescent microscope.
“We were surprised to find many more abnormal circulating cells in
lung cancer patients compared with what had been seen previously using
other techniques,” Katz said.
The researchers used 12 biomarker probes that target aberrations
previously connected to lung cancer to analyze 59 cases of non-small
cell lung cancer and 24 controls, people without lung cancer, including
smokers and non-smokers. Their findings include:
- Highly significant differences in the average number of abnormal
cells in the bloodstream between patients and controls. For example,
deletion of a gene at an address on chromosome 3 called 3p22.1 occurred
on average in 7.04 cells per micro liter of blood in controls, while
cases averaged 45.52 cells per micro liter with that deletion.
- Abnormal cells were significantly associated with disease stage,
with cells that contained certain abnormalities increasing
significantly as cancer progressed from early to advanced stage disease.
- Eight of the biomarkers had a strong overall correlation between
abnormal circulating cells and tumors. Chromosomal gain of the EGFR
gene in circulating cells was significantly associated with the same
gain in tumors, most notably among patients with stage III or stage IV
disease.
Some biomarkers were associated with lung cancer recurrence and
overall survival, but none were statistically significant after
adjusting for age, sex and disease stage. Larger clinical trials are
needed to address these associations, Katz said.
The FISH analysis used by the team detected more circulating
abnormal cells – by orders of magnitude – than existing methods that
rely on immunomagnetic beads to attach to an antibody found on the
surface of circulating cells that originate in an organ’s epithelium.
Epithelial tissue lines the surfaces and cavities of organs and 80
percent of all solid tumor cancers originate in the epithelium.
Detection methods for circulating tumor cells have focused strictly on
epithelial cells.
While the FISH analysis detected up to 45,000 abnormal cells per
milliliter of blood, studies using the antibody-based epithelial method
typically find fewer than 10 abnormal cells per milliliter.
Katz believes part of the difference is that FISH is not limited to
epithelial cells, so it picks up mesenchymal cells, thought to be
involved in the spread of primary cancer to other organs, stem cell
precursor cells and a variety of other cell types in addition to
epithelial cells.
“That’s what differentiates this study from others, we use DNA
probes through FISH to look at chromosomal changes in the cell nucleus,
regardless of the cell’s origin,” Katz said.
Katz said future plans include studies with larger numbers of
patients to validate that circulating abnormal cells are related to
disease stage, relapse and survival. They also will evaluate
epithelial, mesenchymal, stem cell and blood and lymphocyte markers,
combined with FISH, to track down the origin of circulating abnormal
cells and their associated traits.
Work is under way to develop a clinical test based on FISH.
This research was funded by grants and a Cancer Prevention
Fellowship from the National Cancer Institute, by MD Anderson’s
Specialized Program of Research Excellence in Lung Cancer grant from
the NCI and a grant from AstraZeneca.
Study co-authors from MD Anderson are Weigong He, Abha Khanna,
Ricardo Fernandez, Tanweer M. Zaidi, Nancy Caraway, M.D., and Hua-Zhong
Zhang of the Department of Pathology; Margaret Spitz, M.D., Carol
Etzel, Ph.D., and Randa El-Zein, M.D., Ph.D. of the Department of
Epidemiology; Stephen Swisher, M.D., Reza J. Mehran, M.D., and Jack
Roth, M.D., of the Department of Thoracic and Cardiovascular Surgery;
Carlos Jimenez, M.D., of the Department of Pulmonary Medicine; and
Jeffrey Morris, Ph.D., of the department of Biostatistics. David
Blowers, Ph.D., of AstraZeneca in Cheshire, UK; Matthew Krebs of
Paterson Institute for Cancer Research in Manchester, UK, and Feng
Jiang, M.D., Ph.D., of the University of Maryland School of Medicine.
The University of Texas MD Anderson Cancer Center and its
researchers have filed patents on the technology and other intellectual
property reported in these papers. If licensing or commercialization of
such intellectual property occurs, the researchers and MD Anderson may
be entitled to financial consideration, including royalties. MD
Anderson manages these relationships in accordance with appropriate
statutes, rules, regulations and policies.
(No Ratings Yet)
Loading …
Posted in 
Add to Google