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RhoC: Early Warning Sign for Aggressive Breast Cancer?

Celina Kleer, Sofia Merajver and Kenneth van Golen
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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