DNA Methylation Studies of Biliary Brush Cytology Samples Likely to Aid in Diagnosis of Cholangiocarcinoma
Bret Petersen, MD, MASGE, reviewing Prachayakul V, et al. Gastrointest Endosc 2021 Jul 11.
Establishing a firm diagnosis for indeterminate biliary strictures is often challenging. The current standard of practice is fluoroscopic and cholangioscopic characterization with brush and biopsy sampling for cytology, histology, and fluorescent in situ hybridization (FISH) evaluation, which are highly specific but relatively insensitive for cholangiocarcinoma (CCA). Advanced endoscopic and cellular/pathology assessments have been described. This single-center study sought to determine methylation indices (MIs) for 2 gene promoters (HOXA1 and NEUROG1) of CCA by prospectively performing polymerase chain reaction assessment of DNA extracted from brush cytology specimens acquired at ERCP.
Among 67 patients, 41 were subsequently confirmed to have CCA, and 26 had benign strictures, with equal distributions by age and gender. The following sensitivity and accuracy data were obtained for the MIs and brush cytology and serum CA 19-9 (>100) levels:
MI HOXA1: 95.1%, 82.3%
MI NEUROG1: 90.2%, 89.5%
Brush cytology: 61.5%, 78.1%
CA 19-9: 69.4%, 77.8%
The combination of both MI tests, cytology, and CA 19-9 yielded maximum sensitivity of 97.4%, with associated specificity of 82.4% and accuracy of 91%. Cytology alone was most specific (100%), and MIs plus cytology was most accurate (92.4%). Among 6 patients with confirmed CCA but negative CA 19-9 and cytology, the MIs were positive in 5.
COMMENTAssessment of brush cytology samples for DNA methylation appears promising in this single-center study. Increased sensitivity and accuracy were demonstrated by combining methylation indices with cytology and serum CA 19-9 results. Assessment of methylation indices may be less time-consuming and costly than current reliance upon FISH evaluation or recently described next-generation sequencing of the cellular genome for specific mutations. Comparative validation studies are needed from multiple centers, incorporating patients with varying risks, including primary sclerosing cholangitis.
Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.
CITATION(S)
Prachayakul V, Rugivarodom M, Nopjaroonsri P, et al. Diagnostic power of DNA methylation markers
suggestive of cholangiocarcinoma in ERCP-based brush cytology. Gastrointest Endosc 2021 Jul 11. (Epub ahead of print) (https://doi.org/10.1016/j.gie.2021.07.005)
