Fluorescence in situ hybridization identifies high risk Barrett's patients likely to develop esophageal adenocarcinoma

Abstract

SUMMARY Barrett’s esophagus (BE) with high-grade dysplasia (HGD) defines a group of individuals at high risk of progression to esophageal adenocarcinoma (EA). Fluorescence in situ hybridization (FISH) has been shown to be useful for the detection of dysplasia and EA in endoscopic brushing specimens from BE patients. The aim of this study was to determine whether FISH in combination with histological findings would further identify more rapid progressors to EA. This is a retrospective cohort study of high-risk patients, having a history of biopsy-confirmed HGD without EA, with an endoscopic brushing specimen analyzed by FISH while undergoing endoscopic surveillance and treatment between April 2003 and October 2010. Brushing specimens were assessed by FISH probes targeting 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) and evaluated for the presence of polysomy, defined as multiple chromosomal gains (displaying ≥ 3 signals for ≥ 2 probes). Specimens containing ≥ 4 cells exhibiting polysomy were considered polysomic. HGD was confirmed by at least two experienced gastrointestinal pathologists. Of 245 patients in this study, 93 (38.0%) had a polysomic FISH result and 152 (62.0%) had a non-polysomic FISH result. Median follow-up was 3.6 years (interquartile range [IQR] 2–5 years). Patients with a polysomic FISH result had a significantly higher risk of developing EA within 2 years (14.2%) compared with patients with a non-polysomic FISH result (1.4%, P < 0.001). These findings suggest that a polysomic FISH result in BE patients with simultaneous HGD identifies patients at a higher risk for developing EA compared with those with non-polysomy.

A Multicenter Study of a Fluorescence In Situ Hybridization Probe Set for Diagnosing High-Grade Dysplasia and Adenocarcinoma in Barrett’s Esophagus

“…Additionally, recent evidence has suggested that FISH may play a role in risk-stratifying individuals with dysplasia. A retrospective analysis of patients with HGD found that if more than 4 of 100 cells had evidence of polysomy, there was a higher likelihood of progression to EA [22]. Although further verification is needed, these findings suggest that genetic changes detected by FISH can both predict HGD lesions elsewhere in the esophageal column as well as progression to EA.…”

Advances in the diagnosis and surveillance of Barrett’s esophagus (with videos)

“…Prior studies have evaluated FISH probes directed against tumor suppressor and proto-oncogenes, such as 8q24 (c-MYC), 9p21 (p16), 17q11.2 (HER2/neu), 17q13.1 (p53), and 20q13.2 (ZNF217) in various BE populations. 44 FISH assays can be performed by using commercially available kits available through multiple companies and tertiary-care centers. These assays are being used in practice to aid in risk stratification of patients with BE for progression to esophageal cancer.…”

“…[46][47][48] The utility of FISH to risk-stratify patients with HGD who will progress to EAC also has been evaluated. 44 In a singlecenter retrospective study, 245 patients with prior biopsyproven HGD without EAC underwent brush cytology during surveillance endoscopy. The authors evaluated the brushing specimens by using the previously described Vysis 4-probe panel for the presence of polysomy; 93 patients (38%) had polysomy detected in at least 1 target gene, and 152 patients (62%) did not.…”

“…Patients with a polysomic FISH result had a significantly higher risk of developing EAC within 2 years (14.2 vs 1.4%; P < .001). 44 FISH also has been studied to predict the response to treatment of BE neoplasia. A retrospective cohort study evaluated 181 patients who underwent endoscopic therapy for HGD or early EAC.…”

MicroRNA Expression Signatures During Malignant Progression From Barrett's Esophagus

“…In the Stachler study, the number of gene amplifications defined by ploidy > 3 increased to 8.44 per EAC sample compared to 0.42 per non‐dysplastic BE sample [Stachler et al, ]. The usefulness of global measures of aneuploidy and chromosomal changes [Li et al, ; Nones et al, ; Timmer et al, ] and established FISH panels [Brankley et al, ] need to be compared against panels of somatic microRNA gene alterations; this comparison will require collaborative studies to reach the necessary sample sizes.…”