RhoC: Early Warning Sign for Aggressive Breast Cancer?

Celina Kleer,
Sofia Merajver and Kenneth van Golen
Photo: Marcia
Ledford |
RhoC, a protein found in breast tumors, could someday help doctors and patients
spot potentially metastatic breast cancer before it begins to spread. A test
to detect the protein is still more than a year away from clinical trials. But
research at the U-M’s Comprehensive Cancer Center shows that RhoC could
be a marker for breast tumors that are most likely to spread or metastasize
— identifying them when they are less than one centimeter in diameter.
U-M scientists developed the test based on their prior research on the RhoC
gene. They evaluated its effectiveness as a cancer marker in 182 tissue samples
from 164 patients whose breasts had been biopsied at U-M, as well as information
about whether they had cancer or benign breast disease like fibrocystic changes.
The RhoC test detected invasive cancer with the potential to metastasize with
88 percent specificity, and with 92 percent specificity for tiny tumors that
had already metastasized. In contrast, samples of normal breast tissue, benign
breast cysts, or non-invasive breast cancer contained little RhoC. U-M scientists
presented their results at an April meeting of the American Association for
Cancer Research.
“RhoC is a very promising marker for small, but invasive breast cancers,
which are hard to identify,” says Celina Kleer, M.D. (Residency 1999),
an assistant professor of pathology in the U-M Medical School who specializes
in breast cancer. “While more research is needed before clinical testing
can begin, we hope RhoC will help identify early-stage cancer that could be
vulnerable to aggressive treatment.”
Kleer and her U-M colleagues — including Sofia Merajver (M.D. 1987, Residency
1993), Ph.D., associate professor of internal medicine, and Kenneth van Golen,
Ph.D., assistant professor of internal medicine — designed the study to
find out how much RhoC was produced in different kinds of breast cancer cells
compared with normal breast cells.
“We found RhoC only in invasive cancers, and almost always correlated
with the presence of metastases. Very few non-metastatic cancers contained high
levels of RhoC,” Kleer says. “The level of RhoC expression also
increased as the stage of the breast cancer increased, which is another confirmation
that it’s a marker of more aggressive cancer. We had enough samples from
invasive metastatic cancers of less than one centimeter in size to show that
RhoC is highly specific for those tumors, but we’d like to look at more
samples to be sure.”
Kleer, Merajver, van Golen and their colleagues are preparing to examine more
breast tissue samples for the presence of RhoC, to see if their initial results
hold up. The team also is planning clinical studies to test the predictive power
of RhoC.
The study was funded by the National Institutes of Health, the Department of
Defense’s breast cancer research program, and a grant from the John and
Suzanne Munn Endowment at the U-M Comprehensive Cancer Center. Additional collaborators
on the study were Zhi-Fen Wu, M.D., and Yanhong Zhang, Ph.D., U-M research associates;
and Mark Rubin, M.D., an associate professor of pathology and urology in the
Medical School.
—KG
Read the complete story at:
www.med.umich.edu/opm/newspage/2002/breastcancer.htm
For more information on RhoC:
www.cancer.med.umich.edu/news/genenews.htm
For more information on breast cancer:
www.cancer.med.umich.edu/learn/breastinfo.htm
 
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