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

Abstract Context.—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.” Design.—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 ...