Test predicts cancer in pancreas cysts

JOHNS HOPKINS (US) — A gene-based test can distinguish precancerous pancreatic cysts from harmless ones and may eventually help patients avoid unneeded and potentially risky surgery.

“There has long been a need for accurate, quantitative ways to identify cysts that are more worrisome and to help patients avoid unnecessary surgeries for harmless cysts,” says Bert Vogelstein, professor of oncology and pathology at Johns Hopkins University.

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Fluid-filled cysts are identified each year in more than a million patients, most of whom have undergone CT or MRI scans to evaluate non-specific symptoms, such as abdominal pain and swelling.

“Most cysts are benign,” says Ralph Hruban, professor of pathology and oncology “but distinguishing between the harmless and dangerous ones is challenging for doctors and patients alike.”

For the study, reported in the journal Science Translational Medicine, researchers analyzed precancerous cysts from 19 patients, searched for mutations in 169 cancer-causing genes, and found mutations in the KRAS gene, well-known for its prevalence in pancreatic cancers, and the GNAS gene, which had not previously been associated with pancreatic cancer.

The scientists then tested a total of 132 precancerous pancreatic cysts for mutations in KRAS and GNAS. Nearly all—127—had mutations in GNAS, KRAS or both. The mutations occurred in large and small, high- and low-grade cysts, and in all major types of the most common precancerous pancreatic cysts.

GNAS and KRAS mutations were not found in benign cysts.

Generally, patients with a cyst that appears harmless and is less than 3 centimeters in size are monitored to watch for growth of the cyst or other concerning features such as a solid nodule.

With cysts that appear more worrisome, surgical removal is often recommended, but the procedure requires removal of a portion of the pancreas as well, and complications like a pancreatic fistula (fluid from the pancreas leaks through the surgical incision), eating difficulties, and prolonged recovery can develop.

CT scans, MRI imaging, and enzyme and secreted antigen levels in cyst fluid are imprecise markers for precancerous potential, says Christopher Wolfgang, assistant professor of surgery.
Genetic analysis of the kind reported in the new study offers a new way to sort the potential of cysts to cause malignant trouble.

Cyst fluid removal, an invasive procedure, also has its caveats and can cause bleeding, infection and inflammation in a very small percentage of patients.

Further studies on a larger number of patients must be done before the gene-based test can be widely offered. Vogelstein says, but the technology for developing a gene-based test in this case is relatively straightforward because “the mutation occurs at one spot in both of the genes.”

Funding for the study was provided by the Lustgarten Foundation, the Virginia and D.K. Ludwig Fund for Cancer Research, the Sol Goldman Center for Pancreatic Cancer Research, the Joseph L. Rabinowitz Fund, the Michael Rolfe Foundation, the Indiana Genomics Initiative of Indiana University, the J.C. Monastra Foundation, Swim Across America, and the National Institutes of Health.

Researchers from Indiana University and the Memorial Sloan-Kettering Cancer Center contributed to the research.

More news from Johns Hopkins University: http://releases.jhu.edu/