Zachary M Callahan1, Wennuan Liu2, Jun Hou2, S Lilly Zheng2, Jamaal Rehman3, H Mason Hedberg4, Craig S Brown4, Bailey Su4, Mikhail Attaar4, Kristine Kuchta5, MaryAnn Regner3, JoAnn Carbray4, Jianfeng Xu2, Michael Ujiki4. 1. Department of Surgery, NorthShore University HealthSystem, 2650 Ridge Avenue, GCSI Suite B665, Evanston, IL, 60201, USA. zmcallahan@gmail.com. 2. Program for Personalized Cancer Care and Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA. 3. Department of Pathology, NorthShore University HealthSystem, Evanston, IL, USA. 4. Department of Surgery, NorthShore University HealthSystem, 2650 Ridge Avenue, GCSI Suite B665, Evanston, IL, 60201, USA. 5. Bioinformatics and Research Core, NorthShore University HealthSystem, Evanston, IL, USA.
Abstract
BACKGROUND: The purpose of this study was to analyze non-dysplastic Barrett's esophagus (NDBE) biopsy tissue and compare the rate of somatic DNA copy number alterations (CNAs) in patients who subsequently progressed to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) to those patients who did not. METHODS: A retrospectively collected database of Barrett's esophagus (BE) patients spanning a 16-year period was queried. Patients who progressed from NDBE to HGD or EAC were identified and compared to patients who did not. Initial biopsy specimens were microdissected and extracted DNA underwent Multiplex Ligation-dependent Probe Amplification (MLPA) for CNAs. Comparisons between progressors and non-progressors were made with Fisher's exact and two-sample t tests. Logistic regression assessed factors associated with progression. RESULTS: Of the 2459 patients in the BE database, 36 patients progressed from NDBE to either HGD or EAC. There were eight progressors who had biopsy specimens with adequate DNA for analysis. The progressor and non-progressor cohort had similar demographic information and medical history. The progressor group trended towards being older at diagnosis (72 ± 10 vs. 64 ± 13 years, p = 0.097) and fewer progressors reported reflux symptoms (50 vs. 94.7%, p < 0.001). Progressor specimens had more overall CNAs (75% vs. 33.6%, p = 0.026). On univariable analysis, there was an association between progression and absence of GERD symptoms (OR 16.54 [3.42-80.03], p = 0.001), any CNA (OR 5.10 [1.18-23.30], p = 0.035), and CNA in GATA6 or ERBB2 (OR 6.72 [1.18-38.22], p = 0.032). CONCLUSIONS: Patients who progressed from NDBE to HGD or EAC were older at first diagnosis of BE and fewer of the progressors reported symptoms of reflux when compared to non-progressors. Progression was associated with the presence of any CNA and specific CNAs in GATA6 or ERBB2.
BACKGROUND: The purpose of this study was to analyze non-dysplastic Barrett's esophagus (NDBE) biopsy tissue and compare the rate of somatic DNA copy number alterations (CNAs) in patients who subsequently progressed to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) to those patients who did not. METHODS: A retrospectively collected database of Barrett's esophagus (BE) patients spanning a 16-year period was queried. Patients who progressed from NDBE to HGD or EAC were identified and compared to patients who did not. Initial biopsy specimens were microdissected and extracted DNA underwent Multiplex Ligation-dependent Probe Amplification (MLPA) for CNAs. Comparisons between progressors and non-progressors were made with Fisher's exact and two-sample t tests. Logistic regression assessed factors associated with progression. RESULTS: Of the 2459 patients in the BE database, 36 patients progressed from NDBE to either HGD or EAC. There were eight progressors who had biopsy specimens with adequate DNA for analysis. The progressor and non-progressor cohort had similar demographic information and medical history. The progressor group trended towards being older at diagnosis (72 ± 10 vs. 64 ± 13 years, p = 0.097) and fewer progressors reported reflux symptoms (50 vs. 94.7%, p < 0.001). Progressor specimens had more overall CNAs (75% vs. 33.6%, p = 0.026). On univariable analysis, there was an association between progression and absence of GERD symptoms (OR 16.54 [3.42-80.03], p = 0.001), any CNA (OR 5.10 [1.18-23.30], p = 0.035), and CNA in GATA6 or ERBB2 (OR 6.72 [1.18-38.22], p = 0.032). CONCLUSIONS:Patients who progressed from NDBE to HGD or EAC were older at first diagnosis of BE and fewer of the progressors reported symptoms of reflux when compared to non-progressors. Progression was associated with the presence of any CNA and specific CNAs in GATA6 or ERBB2.
Entities:
Keywords:
Barrett’s esophagus; Esophageal adenocarcinoma; Progression; Somatic copy number alterations
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