Assessment of chromosomal gains as compared to DNA content changes is more useful to detect dysplasia in Barrett's esophagus brush cytology specimens

Abstract

Abnormal DNA ploidy status has been suggested as a prognostic factor for Barrett's esophagus progression into esophageal adenocarcinoma (EAC). The aim of the study was to compare image cytometry DNA analysis (ICDA) and fluorescent in situ hybridization (FISH) in the assessment of DNA ploidy status in Barrett's esophagus (BE), and to determine the value of these abnormalities as an adjunct to conventional cytology in detection of dysplasia and EAC. Brush cytology specimens of 90 BE patients were examined using ICDA and FISH with peri-centromeric probes for chromosomes 7 and 17. The results of ICDA and FISH were compared with each other, and with dysplasia grade or EAC as determined by histology and cytology. FISH and ICDA detected abnormalities in 41% (37/90) and 22% (19/90) of the BE cases, respectively. Gains of chromosome 7 and/or 17 were present in 13% of nondysplasia cases, which further increased with dysplasia stage, while overall DNA content aneuploidy was detected predominantly in high grade dysplasia (HGD) and EAC. Using FISH results combined with cytology, we were able to identify IND/LGD (indefinite/ low grade dysplasia) with a sensitivity and specificity of 75 and 76%, respectively. FISH alone detected HGD/EAC with a high sensitivity and specificity of 85 and 84%, which was superior to that of cytology alone. Thus, FISH is more sensitive than ICDA to detect chromosomal abnormalities in BE brush cytology specimens. FISH detects chromosomal gains in early stages of BE and represents a valuable adjunct to conventional cytology to detect dysplasia or EAC.

Analysis of Dysplasia in Patients With Barrett’s Esophagus Based on Expression Pattern of 90 Genes

“…Dysregulation of c-MYC has been implicated in BE carcinogenesis, 29,30 and its role as a biomarker in BE has been proposed both as an immunohistochemical marker 29,31 and as a fluorescence in situ hybridization probe to detect HGD. [32][33][34] No definite conclusions have yet been made, but previous studies along with this study highlight the importance of revisiting the role of c-MYC in Barrett's carcinogenesis.…”

Developing a Nonendoscopic Screening Test for Barrett‘s Esophagus

“…However, the low sensitivity may be improved by staining for a biomarker specific for BE, and the use of immunohistochemistry, for example [59]. There have been a number of publications concerning the development of novel cytological biomarkers [60][61][62][63][64] for the assessment of dysplasia but few have been performed with the aim to diagnose BE since cytological sampling requires endoscopy.…”

Biomarkers in Barrett's oesophagus

“…One method which is being considered in relation to reducing endoscopic sampling error for dysplasia and OAC is the collection of brush cytology specimens, to improve sampling area, coupled with probes directed against chromosomal abnormalities. Using this FISH (fluorescence in situ hybridization)-based cytology approach coupled with probes directed against chromosomes 7 and 17, Rygiel et al [10] reported high sensitivity (85 %) and specificity (84 %) to detect and distinguish HGD (high-grade dysplasia)/OAC from LGD (low-grade dysplasia)/IND (indefinite dysplasia) and ND (no dysplasia) [10]. It is estimated that OAC develops in Barrett's oesophagus patients at a rate of approx.…”