title: Polysomy and p16 deletion by fluorescence in situ hybridization in the diagnosis of indeterminate biliary strictures.
abstract: BACKGROUND
  The diagnosis of indeterminate biliary strictures is limited because of the low sensitivity of cytology. However, an accurate diagnosis of malignancy is critical in the management of patients with suspected biliary malignancy. Testing for chromosomal aneuploidy by fluorescence in situ hybridization (FISH) may increase the yield.
  
  
  OBJECTIVE
  To evaluate the diagnostic accuracy of FISH in indeterminate biliary strictures and the additional value of including deletion of 9p21 (p16) in the diagnostic criteria of malignant biliary strictures.
  
  
  METHODS
  Retrospective review.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  This study involved 76 consecutive patients who were seen for the evaluation of indeterminate strictures at our institution. These patients were screened, and 50 patients with either a final pathologic diagnosis or ≥ 12 months' conclusive follow-up were included in the analysis.
  
  
  METHODS
  Sensitivity, specificity, and area under the curve (AUC) analysis of cytology alone compared with the presence of FISH polysomy versus FISH polysomy and 9p21 deletion.
  
  
  RESULTS
  The presence of increased copy numbers (polysomy) of chromosome 3, 7, or 17 by FISH increased the sensitivity of brush cytology from 21% to 58%, and when the presence of 9p21 deletion was included, the sensitivity increased to 89%. The specificity of FISH was 97% (vs 100% for cytology). The accuracy of cytology combined with FISH polysomy (AUC = 0.93) or p16 deletion was significantly greater than the accuracy of cytology alone (AUC 0.6; P < .001) or even cytology combined with FISH polysomy (AUC = 0.77; P ≤ .05).
  
  
  CONCLUSIONS
  Sample size. There is a relatively high incidence of malignant biliary strictures in the entire cohort but low incidence among primary sclerosing cholangitis patients, and the majority of cancers are cholangiocarcinomas (as opposed to pancreatic).
  
  
  CONCLUSIONS
  FISH significantly improves the diagnostic accuracy of brush cytology in indeterminate biliary strictures. In our series, the addition of 9p21 deletion to FISH polysomy and cytology further improved sensitivity. This suggests that 9p21 deletion may be added to the diagnostic criteria in indeterminate strictures.
authors.affiliation: Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY, USA. tgonda@gmail.com
authors.forename: Tamas A
authors.initials: TA
authors.lastname: Gonda
authors.forename: Michael P
authors.initials: MP
authors.lastname: Glick
authors.forename: Amrita
authors.initials: A
authors.lastname: Sethi
authors.forename: John M
authors.initials: JM
authors.lastname: Poneros
authors.forename: Walter
authors.initials: W
authors.lastname: Palmas
authors.forename: Shahzad
authors.initials: S
authors.lastname: Iqbal
authors.forename: Susana
authors.initials: S
authors.lastname: Gonzalez
authors.forename: Subhadra V
authors.initials: SV
authors.lastname: Nandula
authors.forename: Jean C
authors.initials: JC
authors.lastname: Emond
authors.forename: Robert S
authors.initials: RS
authors.lastname: Brown
authors.forename: Vundavalli V
authors.initials: VV
authors.lastname: Murty
authors.forename: Peter D
authors.initials: PD
authors.lastname: Stevens
mesh_terms: D000782:Aneuploidy; D019540:Area Under Curve; D001650:Bile Duct Neoplasms / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D001653:Bile Ducts, Intrahepatic / Q000473:pathology*; D018281:Cholangiocarcinoma / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D015209:Cholangitis, Sclerosing / Q000150:complications / Q000175:diagnosis; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D002897:Chromosomes, Human, Pair 7; D002899:Chromosomes, Human, Pair 9; D003251:Constriction, Pathologic / Q000209:etiology / Q000473:pathology; D003581:Cytodiagnosis; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D019942:Genes, p16; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D012372:ROC Curve; D012189:Retrospective Studies
chemical_list: D004273:DNA, Neoplasm