Analysis of microRNA expression in brush cytology specimens improves the diagnosis of pancreatobiliary cancer.


Journal

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
ISSN: 1424-3911
Titre abrégé: Pancreatology
Pays: Switzerland
ID NLM: 100966936

Informations de publication

Date de publication:
Sep 2019
Historique:
received: 18 10 2018
revised: 29 03 2019
accepted: 01 04 2019
pubmed: 12 8 2019
medline: 25 2 2020
entrez: 12 8 2019
Statut: ppublish

Résumé

Malignant pancreatobiliary strictures are in many cases clinically indistinguishable and present a major problem to endoscopy specialists. Intraductal sampling procedures such as brush cytology are commonly used for diagnosis with a sensitivity that is low for a diagnostic test used in daily clinical practice. MicroRNA (miR) alterations detected in many cancers are disease-specific, which can be utilized in clinical applications. The aim of the present study was to analyze whether determination of miR expression levels in intraductal brush cytology specimens is a feasible approach to improve the diagnosis of pancreatobiliary cancer. Brush cytology specimens have been collected during endoscopic retrograde cholangio-pancreatography (ERCP) and analyzed by routine cytology and ancillary miR assays. Total RNA was extracted using the miRNeasy Mini Kit and the expression of miRs frequently dysregulated in pancreatobiliary cancer (miR-16, miR-21, miR-196a, miR-221) were analyzed by quantitative real-time PCR using RNU6B as internal control. Routine cytology resulted in no false positive diagnoses, however, the combined sensitivity remained at 53.8%. Expression (ΔCt values) of miR-16 (p = 0.0039), miR-196a (p = 0.0003) and miR-221 (p = 0.0049) showed a clear statistical significance between malignant and benign pancreatobiliary specimens (n = 35). Malignancy could be detected combining routine cytology and the miR-196a single marker expression levels with a sensitivity of 84.6% (92.9% in biliary strictures) with no false positives. The results offer the first direct demonstration that microRNAs are readily detectable in brush cytology specimens obtained during ERCP, and have the potential to help the cytological diagnosis of pancreatobiliary malignancy.

Sections du résumé

BACKGROUND/OBJECTIVES OBJECTIVE
Malignant pancreatobiliary strictures are in many cases clinically indistinguishable and present a major problem to endoscopy specialists. Intraductal sampling procedures such as brush cytology are commonly used for diagnosis with a sensitivity that is low for a diagnostic test used in daily clinical practice. MicroRNA (miR) alterations detected in many cancers are disease-specific, which can be utilized in clinical applications. The aim of the present study was to analyze whether determination of miR expression levels in intraductal brush cytology specimens is a feasible approach to improve the diagnosis of pancreatobiliary cancer.
METHODS METHODS
Brush cytology specimens have been collected during endoscopic retrograde cholangio-pancreatography (ERCP) and analyzed by routine cytology and ancillary miR assays. Total RNA was extracted using the miRNeasy Mini Kit and the expression of miRs frequently dysregulated in pancreatobiliary cancer (miR-16, miR-21, miR-196a, miR-221) were analyzed by quantitative real-time PCR using RNU6B as internal control.
RESULTS RESULTS
Routine cytology resulted in no false positive diagnoses, however, the combined sensitivity remained at 53.8%. Expression (ΔCt values) of miR-16 (p = 0.0039), miR-196a (p = 0.0003) and miR-221 (p = 0.0049) showed a clear statistical significance between malignant and benign pancreatobiliary specimens (n = 35). Malignancy could be detected combining routine cytology and the miR-196a single marker expression levels with a sensitivity of 84.6% (92.9% in biliary strictures) with no false positives.
CONCLUSIONS CONCLUSIONS
The results offer the first direct demonstration that microRNAs are readily detectable in brush cytology specimens obtained during ERCP, and have the potential to help the cytological diagnosis of pancreatobiliary malignancy.

Identifiants

pubmed: 31400934
pii: S1424-3903(19)30088-2
doi: 10.1016/j.pan.2019.04.001
pii:
doi:

Substances chimiques

MicroRNAs 0
RNA 63231-63-0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

873-879

Informations de copyright

Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Auteurs

N Le (N)

Molecular Gastroenterology Laboratory, 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary; School of PhD Studies, Semmelweis University, Budapest, Hungary.

J Fillinger (J)

Department of Cytopathology, National Institute of Oncology, Budapest, Hungary.

Sz Szanyi (S)

Department of Interventional Gastroenterology, National Institute of Oncology, Budapest, Hungary; School of PhD Studies, Semmelweis University, Budapest, Hungary.

B Wichmann (B)

Molecular Medicine Research Group, Hungarian Academy of Sciences, Budapest, Hungary.

Z B Nagy (ZB)

Molecular Gastroenterology Laboratory, 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.

G Ivády (G)

Department of Cytopathology, National Institute of Oncology, Budapest, Hungary.

M Burai (M)

Department of Interventional Gastroenterology, National Institute of Oncology, Budapest, Hungary.

Á Tarpay (Á)

Department of Interventional Gastroenterology, National Institute of Oncology, Budapest, Hungary.

J Pozsár (J)

Department of Interventional Gastroenterology, National Institute of Oncology, Budapest, Hungary.

Á Pap (Á)

Department of Interventional Gastroenterology, National Institute of Oncology, Budapest, Hungary.

B Molnár (B)

Molecular Gastroenterology Laboratory, 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.

O Csuka (O)

Department of Pathogenetics, National Institute of Oncology, Budapest, Hungary.

M Bak (M)

Department of Cytopathology, National Institute of Oncology, Budapest, Hungary.

Z Tulassay (Z)

Molecular Gastroenterology Laboratory, 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.

R Szmola (R)

Department of Interventional Gastroenterology, National Institute of Oncology, Budapest, Hungary. Electronic address: szmola@gmail.com.

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Classifications MeSH