Barrett's-Associated Neoplasia, Cytology and FISH
Aid to identifying dysplasia and adenocarcinoma in patients with Barrett's esophagus
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Barrett's esophagus is a preneoplastic condition that results in the transformation of benign squamous epithelium of the esophagus into specialized glandular intestinal mucosa. Patients with Barrett's esophagus are at a significantly increased risk for developing esophageal adenocarcinoma and, therefore, require close monitoring. Guidelines recommend periodic endoscopic examination of the esophagus with 4-quadrant biopsies taken every 1 cm to 2 cm of affected esophagus. Currently, histology results are considered the gold standard for diagnosing esophageal dysplasia and adenocarcinoma. However, there are many limitations of biopsy including limited sampling of the affected area, lengthy procedure time for biopsy collection, poor interobserver reproducibility of pathologists to diagnose dysplasia or adenocarcinoma, and an inability of histologic findings to predict patient progression from Barrett's esophagus to esophageal adenocarcinoma.(1)
FISH, a technique that utilizes fluorescently labeled DNA probes to examine cells for chromosomal alterations, can be used to detect cells with chromosomal changes (eg, polysomy) that are indicative of neoplasia (dysplasia or adenocarcinoma). Studies indicate that a multicolor, multitarget FISH assay that utilizes probes to 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2; alias HER-2), and 20q13.2 (ZNF217), is able to detect dysplasia and adenocarcinoma in endoscopic esophageal brushing specimens collected from patients with Barrett's esophagus.(1,2)
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
An interpretive report is provided based on the combination of routine cytology and FISH results.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Negative FISH results do not rule out the presence of dysplasia or adenocarcinoma.
While polysomic FISH results are suggestive of high-grade dysplasia or adenocarcinoma, biopsy confirmation should be obtained before therapeutic interventions are instituted. Patients with a positive FISH result but negative biopsy should be followed closely.
This test cannot distinguish high-grade dysplasia from adenocarcinoma; both have been shown to exhibit the same type of FISH abnormalities.
A study was performed at Mayo Clinic to determine the relative sensitivities and specificities of FISH, conventional cytology, and DNA ploidy analysis with digital image analysis (DIA).(3) This study utilized 119 specimens from 97 patients. Endoscopic histology results were used as the gold standard for determining sensitivity and specificity of the assay. The histologic classification and number of specimens analyzed were as follows: benign squamous epithelium, 24; intestinal metaplasia, 22; low-grade dysplasia (LGD), 25; high-grade dysplasia (HGD), 24; adenocarcinoma, 24. The sensitivity of cytology, DIA, and FISH for LGD was 4%, 8%, and 48% (P < or =0.05); for HGD was 29%, 42%, and 79% (P < or =0.05); and for adenocarcinoma was 42%, 47%, and 89% (P < or =0.05). The specificity of cytology, DIA, and FISH among patients with a corresponding benign squamous epithelium biopsy result of was 88%, 88%, and 96%, respectively, (P=0.51), and was 93%, 93%, and 76%, respectively, among patients with a corresponding biopsy of either benign squamous epithelium or intestinal metaplasia.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Brankley SM, Wang KK, Harwood AR, et al: The development of a fluorescence in situ hybridization assay for the detection of dysplasia and adenocarcinoma in Barrett's esophagus. J Mol Diagn 2006 May;8(2):260-267
2. Rygiel AM, Milano F, Ten Kate FJ, et al: Gains and amplifications of c-myc, EGFR, and 20q13 loci in the no dysplasia-dysplasia-adenocarcinoma sequence of Barrett's esophagus. Cancer Epidermiol Biomarkers Prev 2008;17:1380-1385
3. Barr Fritcher EG, Brankley SM, Kipp BR, et al: A comparison of conventional cytology, DNA ploidy analysis, and fluorescence in situ hybridization for the detection of dysplasia and adenocarcinoma in patients with Barrett's esophagus. Hum Pathol 2008;39:1128-1135