A1 Journal article (refereed)
NGS of brush cytology samples improves the detection of high-grade dysplasia and cholangiocarcinoma in patients with primary sclerosing cholangitis : A retrospective and prospective study (2024)
Boyd, S., Mustamäki, T., Sjöblom, N., Nordin, A., Tenca, A., Jokelainen, K., Rantapero, T., Liuksiala, T., Lahtinen, L., Kuopio, T., Kytölä, S., Mäkisalo, H., Färkkilä, M., & Arola, J. (2024). NGS of brush cytology samples improves the detection of high-grade dysplasia and cholangiocarcinoma in patients with primary sclerosing cholangitis : A retrospective and prospective study. Hepatology Communications, 8(4), Article e0415. https://doi.org/10.1097/HC9.0000000000000415
JYU authors or editors
Publication details
All authors or editors: Boyd, Sonja; Mustamäki, Taru; Sjöblom, Nelli; Nordin, Arno; Tenca, Andrea; Jokelainen, Kalle; Rantapero, Tommi; Liuksiala, Thomas; Lahtinen, Laura; Kuopio, Teijo; et al.
Journal or series: Hepatology Communications
eISSN: 2471-254X
Publication year: 2024
Publication date: 29/03/2024
Volume: 8
Issue number: 4
Article number: e0415
Publisher: Wolters Kluwer Health
Publication country: United States
Publication language: English
DOI: https://doi.org/10.1097/HC9.0000000000000415
Publication open access: Openly available
Publication channel open access: Open Access channel
Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/94478
Publication is parallel published: http://hdl.handle.net/10138/574330
Abstract
Biliary dysplasia, a precursor of cholangiocarcinoma (CCA), is a common complication of primary sclerosing cholangitis. Patients with high-grade dysplasia (HGD) or early CCA who have received oncological treatment are candidates for liver transplantation. The preoperative diagnosis of CCA or HGD is challenging, and the sensitivity of biliary brush cytology (BC) is limited.
Methods:
By using next-generation sequencing (NGS), we retrospectively analyzed archived tissue samples (n=62) obtained from explanted liver tissue and CCA samples to identify oncogenic mutations that occur during primary sclerosing cholangitis carcinogenesis. BC samples were prospectively collected from patients with primary sclerosing cholangitis (n=97) referred for endoscopic retrograde cholangiography to measure the diagnostic utility of NGS combined with BC compared with traditional cytology alone.
Results:
Mutations in KRAS, GNAS, FLT3, RNF43, TP53, ATRX, and SMAD4 were detected in archived CCA or HGD samples. KRAS, GNAS, TP53, CDKN2A, FBXW7, BRAF, and ATM mutations were detected in prospectively collected brush samples from patients with histologically verified CCA or HGD. One patient with low-grade dysplasia in the explanted liver had KRAS and GNAS mutations in brush sample. No mutations were observed in brush samples or archived tissues in liver transplantation cases without biliary neoplasia. While KRAS mutations are common in biliary neoplasms, they were also observed in patients without biliary neoplasia during surveillance.
Conclusions:
In summary, NGS of BC samples increased the sensitivity of detecting biliary neoplasia compared with traditional cytology. Performing NGS on BC samples may help diagnose HGD or early CCA, benefiting the timing of liver transplantation.
Keywords: liver diseases; cancerous diseases; sclerosing cholangitis; carcinomas; dysplasia; diagnostics; liver transplantation; treatment methods; cell biology
Contributing organizations
Ministry reporting: Yes
Preliminary JUFO rating: 1
