title: Analysis of loss of heterozygosity in atypical and negative bile duct brushing cytology specimens with malignant outcome: are "false-negative" cytologic findings a representation of morphologically subtle molecular alterations?
abstract: BACKGROUND
  Conventional cytologic evaluation of bile duct brushings for neoplasia has high specificity but relatively low sensitivity.
  
  
  OBJECTIVE
  The aim of this pilot study was to examine whether K-ras mutations and loss of heterozygosity for multiple microsatellite markers in bile duct brushings would contribute to the detection of malignancy in cases initially reported as "negative" or "atypical."
  
  
  METHODS
  Bile duct brushing specimens with a negative or an atypical cytologic result (9 cases) had a benign result on the surgical pathology specimen, and 9 additional negative or atypical cases demonstrated adenocarcinoma on the resected surgical specimen. Cells from representative cytopathology and histology slides were microdissected and analyzed for K-ras mutations and for loss of heterozygosity with a panel of 15 polymorphic markers on chromosomes 1p, 3p, 5q, 9p, 9q, 10q, 17p, and 22q.
  
  
  RESULTS
  Among cytology cases with malignant outcome, loss of heterozygosity or K-ras mutation was detected in 8 (88.8%) of 9 cases. In the corresponding 9 surgical pathology specimens with adenocarcinoma, K-ras mutations and/or allelic losses were detected in all (100%). Loss of heterozygosity or K-ras mutation was not detected in cytology cases that had a benign surgical outcome. The fractional allelic loss of these 9 cytology specimens ranged from 0 to 0.25 (mean, 0.14). This compared with the fractional allelic loss ranging from 0.15 to 0.42 (mean, 0.27) for the corresponding surgical specimens.
  
  
  CONCLUSIONS
  This pilot study suggests that low-level fractional allelic loss or K-ras mutation in the negative/atypical cytology samples with malignant outcome is a representation of morphologically subtle molecular alterations.
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center-Presbyterian, Pittsburgh, PA 15213, USA.
authors.forename: Uma
authors.initials: U
authors.lastname: Krishnamurti
authors.forename: Eizaburo
authors.initials: E
authors.lastname: Sasatomi
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Swalsky
authors.forename: Sydney D
authors.initials: SD
authors.lastname: Finkelstein
authors.forename: N Paul
authors.initials: NP
authors.lastname: Ohori
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D004273:DNA, Neoplasm / Q000235:genetics; D005188:False Negative Reactions; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010865:Pilot Projects; D011379:Prognosis; D012680:Sensitivity and Specificity
chemical_list: D004273:DNA, Neoplasm