Mayo Clinic Researchers Develop Biomarker Panel to Help Predict Outcome for Kidney Cancer Patients Following Surgery

Friday, May 15, 2009

JACKSONVILLE, Fla. — Researchers at Mayo Clinic have developed a way to help physicians more accurately determine which patients with clear cell renal cell carcinoma (ccRCC) will eventually die as a result of their cancer. At the same time, the team of researchers in Florida and Minnesota has also provided additional insight into the molecular factors that drive ccRCC aggressiveness, highlighting potential avenues for the development of new targeted therapies for these patients.

In the May 15 issue of Cancer, the Mayo Clinic researchers used tumor specimens and data on 634 ccRCC patients who underwent surgery at Mayo Clinic to report that the levels of three proteins (survivin, B7-H1, ki-67) in ccRCC tumor tissue can be used to predict which patients will ultimately die from their cancer. They also say that the prognostic information provided by each of these three proteins appeared to be independent of one another. In other words, each biomarker provided useful prognostic information about patient outcome even after the researchers considered the information already provided by the other two.

"Identifying a single biomarker that can provide useful prognostic information is great. Identifying three biomarkers that all provide prognostic information independent of each other is a real opportunity," says the study's lead investigator, Alexander Parker, Ph.D., an Assistant Professor of Epidemiology.

This cancer is the most common to develop in the kidney. Last year alone there were over 40,000 ccRCC tumors diagnosed in the United States and this number has been steadily rising for several decades. The majority of ccRCC patients are diagnosed with tumors that appear to be confined within the kidney and can therefore be cured by surgery. But roughly 30% of patients undergoing surgery will experience a recurrence of their cancer at a distant site, and less than 10% of these patients will survive 5 years, Dr. Parker says.

"Based on this, a key issue for researchers has been identifying ways to more accurately predict which ccRCC patients are at greatest risk of dying from a recurrence of their cancer following surgery," he says.

In this study, the researchers combined the three biomarkers into a novel biomarker panel test, which they call BioScore. They found that patients with the highest BioScore values were five times more likely to die from the cancer compared with patients with low BioScore values.

The researchers say that this novel test, which requires further validation in other patient groups, will be most useful in those situations where patients and their physicians are "on the fence" with regard to their prognosis following surgery. "The current tools physicians have for predicting ccRCC patient outcome are very good, but even so there are instances where the patient's risk of cancer recurrence following surgery is deemed to be 'intermediate' or 'moderate'," Dr. Parker says. "We feel in these situations this test could provide additional peace of mind to some patients, while highlighting potential hidden danger to others."

In addition, by helping to more accurately identify high risk patients, Dr. Parker points out that BioScore has the potential to advance research as well by improving the design of future clinical trials in ccRCC.

"This is a good step forward toward the ultimate goal of individualized care for patients with kidney cancer," he says. "Patients find little comfort in being told there is a chance their cancer may return. They want, and deserve, a more accurate prognosis, and we believe we are on track to provide that."

Still, Dr. Parker says, "until we have effective treatments to offer these patients, telling them their risk of recurrence is high is only doing half the job. But now that we are pinpointing the molecular pathways that have gone awry and are potentially supporting the growth and spread of ccRCC, these same biomarkers can now be studied further to develop new therapies that could be used in combination with surgery to further reduce the chances of cancer recurrence."

Ultimately, Mayo Clinic researchers want to expand BioScore into a panel of 10-12 biomarkers.

"With this study, we have shown that the overall concept of BioScore is achievable. We can identify multiple biomarkers in ccRCC tissues whose expression levels can be combined together into a single scoring system to predict ccRCC patient outcome," Dr. Parker says.

Mayo Clinic holds a patent on development of BioScore, and some of the authors of the study, including Dr. Parker, have filed patent applications pertaining to the individual cancer biomarkers that the test uses.

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Mayo Clinic is the first and largest integrated, not-for-profit group practice in the world. Doctors from every medical specialty work together to care for patients, joined by common systems and a philosophy of "the needs of the patient come first." More than 3,700 physicians, scientists and researchers, and 50,100 allied health staff work at Mayo Clinic, which has campuses in Rochester, Minn; Jacksonville, Fla; and Scottsdale/Phoenix, Ariz.; and community-based providers in more than 70 locations in southern Minnesota., western Wisconsin and northeast Iowa. These locations treat more than half a million people each year. To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news. For information about research and education, visit www.mayo.edu. MayoClinic.com (www.mayoclinic.com) is available as a resource for your health stories.