المتخصصون في المجالات الطبية

Aug. 26, 2026

Malignant pancreatobiliary tumors typically present as strictures in the extrahepatic bile ducts. But patients are often asymptomatic in the early stages of disease, resulting in delayed diagnosis and poor survival rates. When testing does occur, distinguishing between malignant and benign biliary structures can be challenging. Up to 20% of these strictures are classified as indeterminate after initial cytological evaluation of biliary brushings, the current standard of care.

Improvements in diagnosis have been achieved with optimized fluorescence in situ hybridization (FISH). That laboratory technique uses fluorescently labeled DNA probes to detect chromosomal abnormalities in tumor cells. But widespread use of pancreatobiliary FISH testing has been limited by the need for expert handling and interpretation of samples.

Methylated DNA markers (MDMs) have emerged as an easier method of detecting malignant biliary strictures. Mayo Clinic Laboratories plans to offer a new methylation test — known as BMETH — for detecting malignant biliary strictures in biliary brushings. The test was developed in conjunction with Mayo Clinic digestive disease physician-researchers.

As described in Hepatology, Mayo Clinic researchers identified four top candidate markers for malignant biliary strictures: TWIST1, HOXA1, VSTM2B and CLEC11A. The researchers found that a test panel combining the four markers outperformed both cytology and FISH.

The BMETH panel was further validated in a prospective study of Mayo Clinic patients undergoing endoscopic retrograde cholangiopancreatography for biliary strictures. Biliary brushing specimens were split for cytology and pancreatobiliary FISH testing, with BMETH testing performed post-FISH. The final cohort comprised 238 specimens.

Key findings:

• BMETH and FISH demonstrated comparable sensitivity for malignancy detection, both significantly outperforming cytology alone.
• BMETH exhibited significantly higher sensitivity for diagnosing pancreatic adenocarcinoma compared with FISH.
• Sensitivities for extrahepatic cholangiocarcinoma were comparable between BMETH and FISH.
• Sensitivities for primary sclerosing cholangitis (PSC) were comparable between BMETH and FISH, with BMETH specificity exceeding 90% in patients with and without PSC.
• Combining BMETH and FISH results yielded significantly higher sensitivity than either test alone, indicating a complementary diagnostic role.

"Although further validation in multicenter studies is needed, BMETH can serve as a reliable and less resource-intensive alternative to pancreatobiliary FISH," says Manik Aggarwal, M.B.B.S., a gastroenterologist at Mayo Clinic in Rochester, Minnesota. "At Mayo Clinic, pancreatobiliary FISH is offered as a complementary test to routine cytology for detecting biliary malignancies. However, pancreatobiliary FISH isn't widely available at other centers because of the test's high complexity. The methylated DNA marker test is easier to perform and interpret. It represents a significant improvement over routine cytology, either used independently or combined with cytology."

For more information

Cooley MA, et al. Utility of methylated DNA markers for the diagnosis of malignant biliary strictures. Hepatology. 2025;81:453.

Refer a patient to Mayo Clinic.