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

N. Le, J. Fillinger, Sz Szanyi, B. Wichmann, Z. B. Nagy, G. Ivády, M. Burai, Tarpay, J. Pozsár, A. Pap, B. Molnár, O. Csuka, M. Bak, Z. Tulassay, R. Szmola

Research output: Article

1 Citation (Scopus)

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) 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 (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: 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.

Original languageEnglish
Pages (from-to)873-879
Number of pages7
JournalPancreatology
Volume19
Issue number6
DOIs
Publication statusPublished - szept. 1 2019

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MicroRNAs
Cell Biology
Neoplasms
Pathologic Constriction
Routine Diagnostic Tests
Endoscopy
Real-Time Polymerase Chain Reaction
RNA

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Cite this

Analysis of microRNA expression in brush cytology specimens improves the diagnosis of pancreatobiliary cancer. / Le, N.; Fillinger, J.; Szanyi, Sz; Wichmann, B.; Nagy, Z. B.; Ivády, G.; Burai, M.; Tarpay; Pozsár, J.; Pap, A.; Molnár, B.; Csuka, O.; Bak, M.; Tulassay, Z.; Szmola, R.

In: Pancreatology, Vol. 19, No. 6, 01.09.2019, p. 873-879.

Research output: Article

Le, N. ; Fillinger, J. ; Szanyi, Sz ; Wichmann, B. ; Nagy, Z. B. ; Ivády, G. ; Burai, M. ; Tarpay ; Pozsár, J. ; Pap, A. ; Molnár, B. ; Csuka, O. ; Bak, M. ; Tulassay, Z. ; Szmola, R. / Analysis of microRNA expression in brush cytology specimens improves the diagnosis of pancreatobiliary cancer. In: Pancreatology. 2019 ; Vol. 19, No. 6. pp. 873-879.
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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) 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 (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: 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.",
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T1 - Analysis of microRNA expression in brush cytology specimens improves the diagnosis of pancreatobiliary cancer

AU - Le, N.

AU - Fillinger, J.

AU - Szanyi, Sz

AU - Wichmann, B.

AU - Nagy, Z. B.

AU - Ivády, G.

AU - Burai, M.

AU - Tarpay,

AU - Pozsár, J.

AU - Pap, A.

AU - Molnár, B.

AU - Csuka, O.

AU - Bak, M.

AU - Tulassay, Z.

AU - Szmola, R.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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) 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 (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: 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.

AB - 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) 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 (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: 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.

KW - Bile duct cancer

KW - ERCP

KW - Intraductal sampling

KW - miRNA

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