Comparison of KRAS mutation analysis and FISH for detecting pancreatobiliary tract cancer in cytology specimens collected during endoscopic retrograde cholangiopancreatography

Benjamin R. Kipp, Emily G. Barr Fritcher, Amy C. Clayton, Gregory James Gores, Lewis Rowland Roberts, Jun Zhang, Michael J. Levy, Kevin C. Halling

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Abstract

Pancreatobiliary tract strictures result either from malignancies of the biliary tract and pancreas or from nonmalignant etiopathogenesis. The goal of this study was to determine whether KRAS mutations could be identified in residual pancreatobiliary stricture brushings and to compare the performance characteristics of KRAS mutation analysis to cytology and fluorescence in situ hybridization (FISH) for the detection of carcinoma. Residual brushing cytology cell pellets were retrieved from 132 patients with subsequent clinicopathologic follow-up of cholangiocarcinoma (n = 41), pancreatic adenocarcinoma (n = 35), gallbladder cancer (n = 2), and nonmalignant strictures (n = 54). All specimens had a prior cytology and FISH UroVysion results as part of clinical practice. KRAS mutation analysis was performed using the quantitative PCR DxS KRAS Mutation Test Kit. KRAS mutation analysis was successful in 130 of 132 specimens. KRAS mutations and polysomic (ie, positive) FISH results were identified in 24 (69%) and 22 (63%) pancreatic adenocarcinoma specimens, respectively, with a combined sensitivity of 86% (30/35). KRAS mutations and polysomic FISH results were identified in 12 (29%) and 17 (41%) cholangiocarcinoma specimens, with a combined sensitivity of 54% (22/41). KRAS mutations were identified in two patients with primary sclerosing cholangitis, and benign follow-up. Residual cytology specimens can be used to detect KRAS mutations by quantitative PCR. Combined KRAS mutation and FISH analysis appear to increase the cancer detection rate in patients with pancreatobiliary strictures.

Original languageEnglish (US)
Pages (from-to)780-786
Number of pages7
JournalJournal of Molecular Diagnostics
Volume12
Issue number6
DOIs
StatePublished - Nov 1 2010

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Endoscopic Retrograde Cholangiopancreatography
Fluorescence In Situ Hybridization
Cell Biology
Mutation
Neoplasms
Pathologic Constriction
Cholangiocarcinoma
Adenocarcinoma
Gallbladder Neoplasms
Polymerase Chain Reaction
Sclerosing Cholangitis
Biliary Tract
Pancreas
Carcinoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Pathology and Forensic Medicine

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Comparison of KRAS mutation analysis and FISH for detecting pancreatobiliary tract cancer in cytology specimens collected during endoscopic retrograde cholangiopancreatography. / Kipp, Benjamin R.; Barr Fritcher, Emily G.; Clayton, Amy C.; Gores, Gregory James; Roberts, Lewis Rowland; Zhang, Jun; Levy, Michael J.; Halling, Kevin C.

In: Journal of Molecular Diagnostics, Vol. 12, No. 6, 01.11.2010, p. 780-786.

Research output: Contribution to journalArticle

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abstract = "Pancreatobiliary tract strictures result either from malignancies of the biliary tract and pancreas or from nonmalignant etiopathogenesis. The goal of this study was to determine whether KRAS mutations could be identified in residual pancreatobiliary stricture brushings and to compare the performance characteristics of KRAS mutation analysis to cytology and fluorescence in situ hybridization (FISH) for the detection of carcinoma. Residual brushing cytology cell pellets were retrieved from 132 patients with subsequent clinicopathologic follow-up of cholangiocarcinoma (n = 41), pancreatic adenocarcinoma (n = 35), gallbladder cancer (n = 2), and nonmalignant strictures (n = 54). All specimens had a prior cytology and FISH UroVysion results as part of clinical practice. KRAS mutation analysis was performed using the quantitative PCR DxS KRAS Mutation Test Kit. KRAS mutation analysis was successful in 130 of 132 specimens. KRAS mutations and polysomic (ie, positive) FISH results were identified in 24 (69{\%}) and 22 (63{\%}) pancreatic adenocarcinoma specimens, respectively, with a combined sensitivity of 86{\%} (30/35). KRAS mutations and polysomic FISH results were identified in 12 (29{\%}) and 17 (41{\%}) cholangiocarcinoma specimens, with a combined sensitivity of 54{\%} (22/41). KRAS mutations were identified in two patients with primary sclerosing cholangitis, and benign follow-up. Residual cytology specimens can be used to detect KRAS mutations by quantitative PCR. Combined KRAS mutation and FISH analysis appear to increase the cancer detection rate in patients with pancreatobiliary strictures.",
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AB - Pancreatobiliary tract strictures result either from malignancies of the biliary tract and pancreas or from nonmalignant etiopathogenesis. The goal of this study was to determine whether KRAS mutations could be identified in residual pancreatobiliary stricture brushings and to compare the performance characteristics of KRAS mutation analysis to cytology and fluorescence in situ hybridization (FISH) for the detection of carcinoma. Residual brushing cytology cell pellets were retrieved from 132 patients with subsequent clinicopathologic follow-up of cholangiocarcinoma (n = 41), pancreatic adenocarcinoma (n = 35), gallbladder cancer (n = 2), and nonmalignant strictures (n = 54). All specimens had a prior cytology and FISH UroVysion results as part of clinical practice. KRAS mutation analysis was performed using the quantitative PCR DxS KRAS Mutation Test Kit. KRAS mutation analysis was successful in 130 of 132 specimens. KRAS mutations and polysomic (ie, positive) FISH results were identified in 24 (69%) and 22 (63%) pancreatic adenocarcinoma specimens, respectively, with a combined sensitivity of 86% (30/35). KRAS mutations and polysomic FISH results were identified in 12 (29%) and 17 (41%) cholangiocarcinoma specimens, with a combined sensitivity of 54% (22/41). KRAS mutations were identified in two patients with primary sclerosing cholangitis, and benign follow-up. Residual cytology specimens can be used to detect KRAS mutations by quantitative PCR. Combined KRAS mutation and FISH analysis appear to increase the cancer detection rate in patients with pancreatobiliary strictures.

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