Next-generation sequencing in the evaluation of biliary strictures in patients with primary sclerosing cholangitis.


Journal

Cancer cytopathology
ISSN: 1934-6638
Titre abrégé: Cancer Cytopathol
Pays: United States
ID NLM: 101499453

Informations de publication

Date de publication:
03 2022
Historique:
revised: 06 10 2021
received: 19 08 2021
accepted: 07 10 2021
pubmed: 3 11 2021
medline: 19 4 2022
entrez: 2 11 2021
Statut: ppublish

Résumé

Primary sclerosing cholangitis (PSC) is a well-described risk factor for the development of cholangiocarcinoma (CCA). Early detection of CCA in these patients is of great importance because it expands options for therapeutic interventions, including liver transplantation. Current diagnostic tests for the evaluation of biliary strictures are limited to biliary brushing (BB) cytology and fluorescence in situ hybridization (FISH). Next-generation sequencing (NGS) has become an important diagnostic tool in oncology and may be a useful tool for diagnosing CCA on BBs. It is not clear how NGS performs when it is added to BB cytology and FISH in patients with PSC. This study reports the authors' experience with NGS performed as a prospective cotest with cytology and FISH on BBs obtained from 60 patients with PSC followed at Massachusetts General Hospital. A duct with malignancy was defined as a high-risk (HR) stricture with either high-grade dysplasia or CCA. NGS was better than FISH and cytology in detecting HR strictures, which showed multiple genetic mutations in all cases. NGS provided specific mutational information, and NGS results were reproducible in longitudinal samples. Adding NGS to BB cytology and FISH in the evaluation of biliary strictures for patients with PSC may provide additional information that could help to inform clinical management.

Sections du résumé

BACKGROUND
Primary sclerosing cholangitis (PSC) is a well-described risk factor for the development of cholangiocarcinoma (CCA). Early detection of CCA in these patients is of great importance because it expands options for therapeutic interventions, including liver transplantation. Current diagnostic tests for the evaluation of biliary strictures are limited to biliary brushing (BB) cytology and fluorescence in situ hybridization (FISH). Next-generation sequencing (NGS) has become an important diagnostic tool in oncology and may be a useful tool for diagnosing CCA on BBs. It is not clear how NGS performs when it is added to BB cytology and FISH in patients with PSC.
METHODS
This study reports the authors' experience with NGS performed as a prospective cotest with cytology and FISH on BBs obtained from 60 patients with PSC followed at Massachusetts General Hospital. A duct with malignancy was defined as a high-risk (HR) stricture with either high-grade dysplasia or CCA.
RESULTS
NGS was better than FISH and cytology in detecting HR strictures, which showed multiple genetic mutations in all cases. NGS provided specific mutational information, and NGS results were reproducible in longitudinal samples.
CONCLUSIONS
Adding NGS to BB cytology and FISH in the evaluation of biliary strictures for patients with PSC may provide additional information that could help to inform clinical management.

Identifiants

pubmed: 34726838
doi: 10.1002/cncy.22528
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

215-230

Subventions

Organisme : NIH HHS
ID : 5T32DK007191-45
Pays : United States

Informations de copyright

© 2021 American Cancer Society.

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Auteurs

Johannes F Scheid (JF)

Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts.

Matthew W Rosenbaum (MW)

Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Eric M Przybyszewski (EM)

Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts.

Kumar Krishnan (K)

Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts.

David G Forcione (DG)

Boca Raton Regional Hospital, Boca Raton, Florida.

Anthony J Iafrate (AJ)

Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.

Kyle D Staller (KD)

Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts.

Joseph Misdraji (J)

Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.

Jochen K Lennerz (JK)

Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.

Martha Bishop Pitman (MB)

Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.

Daniel S Pratt (DS)

Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts.
Autoimmune and Cholestatic Liver Center, Massachusetts General Hospital, Boston, Massachusetts.

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