Prediction of response to endoscopic therapy of Barrett’s dysplasia by using genetic biomarkers

Abstract

Background Endoscopic therapy for the treatment of high-grade dysplasia (HGD) and intramucosal cancer (IMC) in Barrett’s esophagus (BE) may not always result in complete remission of dysplasia (CRD). Objective To determine if genetic alterations in the Barrett’s mucosa can predict response to endoscopic therapy. Design Retrospective cohort study. Setting Tertiary-care institution. Patients Selected patients who underwent endoscopic therapy for BE containing HGD/IMC between 2003 and 2010. Interventions Endoscopic therapy combining mucosal resection and different ablation modalities were performed based on patient characteristics, endoscopic findings, and technique evolution. Fluorescence in situ hybridization (FISH) was used to evaluate genetic alterations on baseline endoscopic cytology brushings using probes directed to loci 8q24 (MYC), 9p21 (CDKN2A; alias P16), 17q12 (ERBB2; alias Her-2/neu), and 20q13.2 (ZNF217). Main outcome measurements Genetic biomarkers predicting achievement of CRD after endoscopic therapy. Results A total of 181 patients were included (145 males; age 66 ±10 years). There were 130 patients (72%) who responded to endoscopic therapy with CRD. Multiple gains detected by FISH was found to be a negative predictor (HR 0.57; 95% CI, 0.40-0.82) after adjusting for potential clinical confounders. Similar results were found when analyses were restricted to patients (n = 66) undergoing radiofrequency ablation (HR 0.58; 95% CI, 0.31-1.09). Limitations Retrospective study, heterogeneity of treatment modalities. Conclusion Patients with multiple gains detected by brush cytology specimens may have a lower response rate to endoscopic therapy. The presence of multiple gains can be an adjunct to standard histology in prognosticating BE patients with HGD/IMC undergoing endoscopic therapy.

Diagnostic and Management Implications of Basic Science Advances in Barrett’s Esophagus

“…There were 130 patients (72 %) who responded to endoscopic eradication therapy and achieved complete remission of dysplasia. Multiple gains detected by FISH was found to be a significant negative for achieving this endpoint (hazard ratio 0.57; 95 % CI 0.4 -0.82) [58]. While the results of this study are not conclusive, it paves the path for future studies to evaluate predictive biomarker panels for endoscopic eradication therapy patient selection and surveillance post endoscopic eradication therapy.…”

Chemoprevention in Barrett’s Esophagus

“…In a cohort of 181 patients undergoing radiofrequency ablation, the same FISH panel found that the presence of multiple gains at baseline predicted failure of complete remission of dysplasia (hazard ratio [HR] 0.57, 95% CI 0.40-0.82). 103 As pointed out earlier, if these changes are irreversible, use of these markers may spuriously underestimate the chemopreventive potential of an agent. Contrary to this, epigenetic effects, such as global hypomethylation and promoterspecific hypermethylation that are more dynamic in nature, or microRNA will likely be better markers to assess the efficacy of a chemopreventive agent.…”

Ablative Endoscopic Therapies for Barrett’s-Esophagus-Related Neoplasia

“…[66][67][68] A recent retrospective study showed that the presence of multiple gains detected by brush cytology specimens and FISH was a negative predictor to response rate for endoscopic therapy. 69 Concomitant treatment of acid reflux with PPIs and continuous surveillance are essential for better success outcomes and maintaining the stability of the neosquamous epithelium. However, prior fundoplication did not improve safety and efficacy outcomes for patients undergoing RFA.…”