An Optimized Set of Fluorescence in Situ Hybridization Probes for Detection of Pancreatobiliary Tract Cancer in Cytology Brush Samples

Emily G. Barr Fritcher, Jesse S. Voss, Shannon M. Brankley, Michael B. Campion, Sarah M. Jenkins, Matthew E. Keeney, Michael R. Henry, Sarah M. Kerr, Roongruedee Chaiteerakij, Ekaterina V. Pestova, Amy C. Clayton, Jun Zhang, Lewis Rowland Roberts, Gregory James Gores, Kevin C. Halling, Benjamin R. Kipp

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Background & Aims Pancreatobiliary cancer is detected by fluorescence in situ hybridization (FISH) of pancreatobiliary brush samples with UroVysion probes, originally designed to detect bladder cancer. We designed a set of new probes to detect pancreatobiliary cancer and compared its performance with that of UroVysion and routine cytology analysis. Methods We tested a set of FISH probes on tumor tissues (cholangiocarcinoma or pancreatic carcinoma) and non-tumor tissues from 29 patients. We identified 4 probes that had high specificity for tumor vs non-tumor tissues; we called this set of probes pancreatobiliary FISH. We performed a retrospective analysis of brush samples from 272 patients who underwent endoscopic retrograde cholangiopancreatography for evaluation of malignancy at the Mayo Clinic; results were available from routine cytology and FISH with UroVysion probes. Archived residual specimens were retrieved and used to evaluate the pancreatobiliary FISH probes. Cutoff values for FISH with the pancreatobiliary probes were determined using 89 samples and validated in the remaining 183 samples. Clinical and pathologic evidence of malignancy in the pancreatobiliary tract within 2 years of brush sample collection was used as the standard; samples from patients without malignancies were used as negative controls. The validation cohort included 85 patients with malignancies (46.4%) and 114 patients with primary sclerosing cholangitis (62.3%). Samples containing cells above the cutoff for polysomy (copy number gain of ≤2 probes) were classified as positive in FISH with the UroVysion and pancreatobiliary probes. Multivariable logistic regression was used to estimate associations between clinical and pathology findings and results from FISH. Results The combination of FISH probes 1q21, 7p12, 8q24, and 9p21 identified cancer cells with 93% sensitivity and 100% specificity in pancreatobiliary tissue samples and were therefore included in the pancreatobiliary probe set. In the validation cohort of brush samples, pancreatobiliary FISH identified samples from patients with malignancy with a significantly higher level of sensitivity (64.7%) than the UroVysion probes (45.9%) (P

Original languageEnglish (US)
Pages (from-to)1813-1824e1
JournalGastroenterology
Volume149
Issue number7
DOIs
StatePublished - Dec 1 2015

Keywords

  • Chromosomal Abnormalities
  • Genetics
  • Molecular
  • Tumor

ASJC Scopus subject areas

  • Gastroenterology

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    Barr Fritcher, E. G., Voss, J. S., Brankley, S. M., Campion, M. B., Jenkins, S. M., Keeney, M. E., Henry, M. R., Kerr, S. M., Chaiteerakij, R., Pestova, E. V., Clayton, A. C., Zhang, J., Roberts, L. R., Gores, G. J., Halling, K. C., & Kipp, B. R. (2015). An Optimized Set of Fluorescence in Situ Hybridization Probes for Detection of Pancreatobiliary Tract Cancer in Cytology Brush Samples. Gastroenterology, 149(7), 1813-1824e1. https://doi.org/10.1053/j.gastro.2015.08.046