RESEARCH presented at UEG Week 2024 has demonstrated that using TP53 mutations and chromosomal changes as genomic markers significantly enhances the prediction of oesophageal adenocarcinoma progression in patients with low-risk Barrett’s Oesophagus (BE).
The current surveillance for low-risk BE is inefficient, costly, and highly dependent on subjective histological assessments, which suffer from variability among pathologists. This study aimed to overcome these limitations by identifying genomic markers that could improve risk stratification and guide more individualized care. Specifically, researchers sought to create a clinically relevant targeted sequencing panel to detect genomic features predictive of progression to oesophageal adenocarcinoma in non-dysplastic patients with BE.
In this study, DNA from baseline and prior non-dysplastic biopsies of patients with BE, including 105 progressors and 115 non-progressors, were sequenced to identify mutations and copy number variations (CNVs). The median progression time for the progressor group was 4 years, while non-progressors had a median follow-up of 6 years. Statistical analysis, including logistic regression and mixed-effects models, was used to assess the significance of specific genomic features. The results showed that TP53 mutations were strongly associated with an increased risk of progression (p < 0.0001; HR: 3.84, 95% CI: 2.89-5.67), as was 17p chromosomal loss (p < 0.0001; hazard ratio [HR]: 4.41; 95% CI: 2.29-8.52). Furthermore, patients with both TP53 mutations and 17p loss tended to progress faster. Other factors, such as chromosomal arm CNVs (p = 0.0012, HR = 1.32) and mutational burden (p < 0.0001; HR: 1.30), were also significant. A combined model incorporating these markers achieved 57% sensitivity and 84% specificity with an AUC of 0.758.
These findings demonstrate role of TP53 in the progression of BE, even in the absence of dysplasia, and suggest that a combination of genomic markers could improve current surveillance protocols. Implementing this approach in clinical practice could optimize resource allocation by focusing intensive surveillance on high-risk patients, potentially preventing progression to cancer while reducing unnecessary procedures for those at lower risk.
Katrina Thornber, EMJ
Reference
P Stougie et al. Identifying putative genomic biomarkers for risk stratification in Barrett’s Esophaghus patients with normal histological features. UEG Week 2024, 12-15 October, 2024.
