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Analysis of microrna expression in brush cytology specimens improves the diagnosis of pancreatobiliary cancer
To appear in:
Please cite this article as: Le N, Fillinger J, Szanyi S, Wichmann B, Nagy ZB, Ivády G, Burai M, Tarpay Á, Pozsár J, Pap Á, Molnár B, Csuka O, Bak M, Tulassay Z, Szmola R, Analysis of microrna expression in brush cytology specimens improves the diagnosis of pancreatobiliary cancer, Pancreatology (2019), doi: https://doi.org/10.1016/j.pan.2019.04.001.
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Classification: pancreatic cancer
ANALYSIS OF MICRORNA EXPRESSION IN BRUSH CYTOLOGY SPECIMENS IMPROVES THE
DIAGNOSIS OF PANCREATOBILIARY CANCER.
1 - Department of Interventional Gastroenterology, National Institute of Oncology, Budapest, Hungary; 2 -
Molecular Gastroenterology Laboratory, 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary; 3 - Department of Cytopathology, National Institute of Oncology, Budapest, Hungary; 4 - Department of Pathogenetics, National Institute of Oncology, Budapest, Hungary; 5 - School of PhD studies, Semmelweis University, Budapest, Hungary; 6 - Molecular Medicine Research Group, Hungarian Academy of Sciences, Budapest, Hungary
Running head: microRNA test in brush cytology
Manuscript type: original article
Manuscript information: 15 text pages, 3 figures, 4 tables.
ABSTRACT. Background/Objectives: 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: Brush cytology specimens have been collected during endoscopic retrograde cholangio-pancreatography (ERCP) prospectively 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: Routine cytology resulted in no false positive diagnoses, however, the combined sensitivity remained at 53.8%. Expression (∆Ct 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: 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.