TY - JOUR
T1 - Analysis of loss of heterozygosity in atypical and negative bile duct brushing cytology specimens with malignant outcome
T2 - Are "false- negative" cytologic findings a representation of morphologically subtle molecular alterations?
AU - Krishnamurti, Uma
AU - Sasatomi, Eizaburo
AU - Swalsky, Patricia A.
AU - Finkelstein, Sydney D.
AU - Ohori, N. Paul
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/1
Y1 - 2007/1
N2 - 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 (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.
AB - 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 (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.
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M3 - Article
C2 - 17227126
AN - SCOPUS:33846648625
SN - 0003-9985
VL - 131
SP - 74
EP - 80
JO - Archives of Pathology and Laboratory Medicine
JF - Archives of Pathology and Laboratory Medicine
IS - 1
ER -