TY - JOUR
T1 - Efficient automated assessment of genetic abnormalities detected by fluorescence in situ hybridization on brush cytology in a Barrett esophagus surveillance population
AU - Rygiel, Agnieszka M.
AU - Van Baal, Jantine W.P.M.
AU - Milano, Francesca
AU - Wang, Kenneth K.
AU - Ten Kate, Febo J.
AU - Fockens, Paul
AU - Rosmolen, Wilda D.
AU - Bergman, Jacques J.G.H.M.
AU - Peppelenbosch, Maikel P.
AU - Krishnadath, Kausilia K.
PY - 2007/5/15
Y1 - 2007/5/15
N2 - BACKGROUND. Automated assessment of genetic abnormalities detected by fluorescence in situ hybridization (FISH) in brush cytology specimens from patients with Barrett esophagus (BE) may enhance the clinical applicability of this methodology. The objectives of this study were to validate a novel, automated, proprietary system (CytoVison SPOT AX) for the assessment of FISH abnormalities in BE brush cytology and, subsequently, to use this automated method for screening of a BE surveillance cohort. METHODS. FISH with DNA probes for chromosomes 9, 17, and Y, and for the 9p21 (p16), 17q11.2 (Her2/neu), and 17p13.1 (p53) loci was applied on brush cytology specimens from a surveillance cohort of 151 patients with BE. Validation of the automated system was performed by comparison of the automated FISH results with manual scores for the first 60 patients. RESULTS. There was 98% concordance between manual and automated FISH analysis with κ values from 0.49 to 1 for the different probes. The loss of 17p13.1 (p53) was observed in only 5% of patients with no dysplasia (ND) and in 9% of patients with low-grade dysplasia (LGD) but increased to 46% in patients with high-grade dysplasia (HGD) (P < .005; Fisher exact test). Chromosomes 9 and 17 were observed in 6% of patients with ND, in 21% of patients with LGD, and in 62% of patients with HGD (P < .05). Ten percent of patients with ND had loss of the Y chromosome, which increased to 27% in patients with HGD (P < .05). The amplification of 17q11.2 (Her2/neu) was detected in 62% of patients with HGD (P < .001). CONCLUSIONS. The current investigation indicated that the CytoVison SPOT AX is an objective, efficient system for the analysis of DNA-FISH on BE brush cytology and is applicable for analyzing large populations of BE patients. In the current study cohort, the loss of 17p13.1 (p53), Y chromosome loss, and polysomy of chromosomes 17 and 9 were correlated with increasing grade of dysplasia in patients with BE.
AB - BACKGROUND. Automated assessment of genetic abnormalities detected by fluorescence in situ hybridization (FISH) in brush cytology specimens from patients with Barrett esophagus (BE) may enhance the clinical applicability of this methodology. The objectives of this study were to validate a novel, automated, proprietary system (CytoVison SPOT AX) for the assessment of FISH abnormalities in BE brush cytology and, subsequently, to use this automated method for screening of a BE surveillance cohort. METHODS. FISH with DNA probes for chromosomes 9, 17, and Y, and for the 9p21 (p16), 17q11.2 (Her2/neu), and 17p13.1 (p53) loci was applied on brush cytology specimens from a surveillance cohort of 151 patients with BE. Validation of the automated system was performed by comparison of the automated FISH results with manual scores for the first 60 patients. RESULTS. There was 98% concordance between manual and automated FISH analysis with κ values from 0.49 to 1 for the different probes. The loss of 17p13.1 (p53) was observed in only 5% of patients with no dysplasia (ND) and in 9% of patients with low-grade dysplasia (LGD) but increased to 46% in patients with high-grade dysplasia (HGD) (P < .005; Fisher exact test). Chromosomes 9 and 17 were observed in 6% of patients with ND, in 21% of patients with LGD, and in 62% of patients with HGD (P < .05). Ten percent of patients with ND had loss of the Y chromosome, which increased to 27% in patients with HGD (P < .05). The amplification of 17q11.2 (Her2/neu) was detected in 62% of patients with HGD (P < .001). CONCLUSIONS. The current investigation indicated that the CytoVison SPOT AX is an objective, efficient system for the analysis of DNA-FISH on BE brush cytology and is applicable for analyzing large populations of BE patients. In the current study cohort, the loss of 17p13.1 (p53), Y chromosome loss, and polysomy of chromosomes 17 and 9 were correlated with increasing grade of dysplasia in patients with BE.
KW - Automated fluorescence in situ hybridization analysis
KW - Barrett esophagus
KW - Brush cytology
KW - Cytogenetic abnormalities
UR - http://www.scopus.com/inward/record.url?scp=34248397942&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34248397942&partnerID=8YFLogxK
U2 - 10.1002/cncr.22643
DO - 10.1002/cncr.22643
M3 - Article
C2 - 17385213
AN - SCOPUS:34248397942
SN - 0008-543X
VL - 109
SP - 1980
EP - 1988
JO - Cancer
JF - Cancer
IS - 10
ER -