Comparative molecular analysis of loss of heterozygosity in adenocarcinoma in bile duct brushings and corresponding surgical pathology specimens.
BACKGROUND
Bile duct brushing is the procedure of choice for the assessment of neoplasia of the biliary and pancreatic ducts. Conventional cytopathologic evaluation has been reported to have high specificity but relatively low sensitivity. Although a number of molecular studies regarding biliary tract tissue specimens have been performed, to the authors' knowledge their precise applicability to cytopathology specimens has not been critically analyzed.


METHODS
Bile duct brushing specimens with the cytopathologic diagnosis of "suspicious" or "positive for malignant cells" along with corresponding surgical pathology specimens demonstrating adenocarcinoma were searched for in the files of UPMC-Presbyterian Hospital for the years 1990-1996. Tumor cells from representative cytopathology and histology slides were microdissected and analyzed for loss of heterozygosity (LOH) in a panel of microsatellite markers. The results obtained from cytopathologic and surgical pathology specimens were compared.


RESULTS
Eight paired surgical and cytopathology cases of adenocarcinoma involving the biliary tract were identified. The fractional allelic loss (FAL) for the surgical specimens (FAL-S) ranged from 12.5-71.4% and the FAL for the cytopathology specimens (FAL-C) ranged from 25-71.4%. However, when evaluating the actual loci of LOH, the concordance rate of the surgical and cytopathology specimens ranged from 71.4-100% (mean, 88.6%). Only 3 of the 8 cases (37.5%) were found to have identical matching of the LOH loci.


CONCLUSIONS
Although the overall concordance rate of LOH in biliary cytology and surgical specimens by molecular analysis is relatively high, the issue of molecular tumoral heterogeneity must be considered if clinical decisions are to be based exclusively on cytopathologic analysis.
Ohori
N Paul
NP
Department of Pathology, University of Pittsburgh School of Medicine and UPMC-Presbyterian, Pittsburgh, Pennsylvania 15213, USA. ohorinp@msx.upmc.edu
Fowler
Melissa H
MH
Swalsky
Patricia A
PA
Pal
Rekha
R
Thompson
James
J
Finkelstein
Sydney D
SD
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D001652:Bile Ducts / Q000166:cytology* / Q000473:pathology*; D001661:Biliary Tract Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012189:Retrospective Studies; D007507:Therapeutic Irrigation