Aneusomy detected by fluorescence in-situ hybridization has high positive predictive value for Barrett's dysplasia.
OBJECTIVE
The goal of this study was to pilot a commercial four-colour fluorescence in-situ hybridization (FISH) probe set as a marker of dysplasia in surveillance biopsies.


RESULTS
FISH probes to 9p12 (CDKN2A), 17q11.2-12 (HER2), 8q24.12-13 (CMYC) and 20q13.2 (ZNF217) in 20 cases of Barrett's oesophagus. Dysplastic and non-dysplastic mucosa were compared for each case. Two observers independently counted 50 cells in each region of interest (ROI), and the mean score taken. Wilcoxon's signed-rank test was used to determine the significance of differences between dysplastic and non-dysplastic tissue. Predictive power was determined by logistic regression and receiver operator characteristic (ROC) curves were plotted to examine sensitivity and specificity of each gene to detect dysplasia. Interobserver agreement was excellent. HER2, CMYC and ZNF217 showed significant (P < 0.0005) increases in copy number in dysplastic mucosa; CDKN2A had an insignificant (P = 0.852) decrease when compared to non-dysplastic mucosa. While aneusomy was strongly predictive of dysplasia, eusomy did not rule it out.


CONCLUSIONS
Increased HER2, CMYC and ZNF217 copy number distinguished dysplastic from non-dysplastic mucosa, but non-detection of aneusomy did not exclude dysplasia. Further studies are justified to determine whether FISH-positive dysplasia might justify earlier treatment by radio-frequency ablation.
University of Glasgow, Glasgow, UK.
Euan A G
EA
Allan
Greater Glasgow and Clyde NHS, Glasgow, UK.
Roy
R
Miller
Greater Glasgow and Clyde NHS, University of Glasgow, Glasgow, UK.
James J
JJ
Going
D019540:Area Under Curve; D001471:Barrett Esophagus / Q000175:diagnosis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis*; D018628:Gene Dosage; D018734:Genes, erbB-2; D016259:Genes, myc; D019942:Genes, p16; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D010865:Pilot Projects; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000235:genetics; D012372:ROC Curve; D012680:Sensitivity and Specificity; D015534:Trans-Activators / Q000235:genetics
D014408:Biomarkers, Tumor; D015534:Trans-Activators; C113698:ZNF217 protein, human
Barrett oesophagus; fluorescence in-situ hybridization; gastroesophageal reflux; precancerous conditions