Genetic test shows promise for identifying pancreatic cysts at high risk for cancer

A novel genetic testing strategy developed at University of Pittsburgh Medical Center, which sequences mutations in pancreatic cyst fluid before surgery, showed high accuracy for identifying cysts associated with a high risk for aggressive pancreatic cancer.

These results, recently published in Gut, represent “a critical step toward a precision medicine approach to detecting and treating pancreatic cancer, which has one of the lowest survival rates of all cancers,” according to a press release.

“On the one hand, you never want to subject a patient to unneeded surgery. But survival rates for pancreatic cancer are much better if it is caught before symptoms arise, so you also don’t want to ignore an early warning sign,” Aatur D. Singhi, MD, PhD, a surgical pathologist in the University of Pittsburgh Medical Center division of anatomic pathology, said in the press release. “This rapid, sensitive test will be useful in guiding physicians on which patients would most benefit from surgery.”

Singhi and colleagues developed this testing strategy, called PancreaSeq, which tests for 10 pancreatic cancer-linked tumor genes in a small amount of pancreatic cyst fluid using next-generation sequencing. To evaluate the accuracy of the test, Singhi and colleagues insisted they perform the study in a clinical lab rather than a research setting.

“This was important to us,” Singhi said in the press release. “If PancreaSeq is going to be used to make clinical decisions, then it needed to be evaluated in a clinical setting in real time, with all the pressures that go with a clinical diagnosis.”

Singhi and colleagues prospectively collected 626 pancreatic cyst fluid specimens from 595 patients via endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) during a period of 43 months. Then they performed next generation sequencing on the specimens, and compared the results to EUS-FNA findings, ancillary studies and follow-up data.

They found 49% of the specimens showed KRAS/GNAS mutations, which are “highly specific for intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs).” Additionally, they found 6% of specimens showed TP53/PIK3CA/PTEN alterations, which are “associated with advanced neoplasia.”

Researchers evaluated the accuracy of the test based on follow-up data from 102 patients whose cysts were surgically removed based on current guideline recommendations. Among them, 100% of IPMNs and 30% of MCNs showed KRAS/GNA mutations, and these mutations predicted a mucinous pancreatic cyst with 89% sensitivity and 100% specificity.

The same mutations predicted mucinous cysts with 65% sensitivity and 100% specificity in a separate cohort of 159 specimens evaluated by Sanger sequencing for comparison.

Combining KRAS/GNAS mutations and TP53/PIK3CA/PTEN alterations in the next-generation sequencing test predicted advanced neoplasia with 89% sensitivity and 100% specificity.

The test was less accurate for detecting ductal dilatation, mural nodules and malignant cytopathology.

“Importantly, PancreaSeq did not identify any false positives in either cyst type, making it a highly specific test,” according to the press release.

The researchers said they will further assess the test’s accuracy by following patients who did not have their cysts removed, and are currently evaluating an improved version of the test with additional pancreatic cancer-linked tumor genes.

“Future studies are required to explore the integration of DNA-based molecular testing into current management guidelines,” Singhi and colleagues wrote. – by Adam Leitenberger

Disclosures: The authors report no relevant financial disclosures.