Aberrant p53 expression is associated with higher risk of progression to advanced neoplasia in Barrett's esophagusp53 Expression Linked to Higher Risk of Barrett's Esophagus Progression

The American journal of gastroenterology Published October 8, 2026 Study authors: Sawas Tarek, Davitkov Perica, Zhou Margaret, Eluri Swathi, Leiman David A, Thrift Aaron P, Singh Sid… PubMed ↗ DOI ↗ Editorial oversight: Dr. Lars van Dijk, PhD · Surgical, Procedural & Diagnostic

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Key Takeaway

Note that aberrant p53 expression is associated with a higher risk of progression to advanced neoplasia in Barrett's esophagus.

This meta-analysis synthesized data from 27 studies to evaluate the utility of p53 immunohistochemistry in patients with Barrett's esophagus (BE). The primary objective was to determine the association between aberrant p53 expression and progression to advanced neoplasia, specifically high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC).

Key findings indicate that 20% of patients had aberrant p53 expression at baseline (95% CI: 14%, 27%). The rate of progression was significantly higher in patients with aberrant p53 (8 per 100 person-years; 95% CI: 6, 11) compared to those without (0.3 per 100 person-years; 95% CI: 0.1, 0.6). In cohort studies, the risk for progression to HGD/EAC was higher with aberrant p53 (RR = 10.2; 95% CI: 6.9, 15.0), and in case-control studies, the risk was also higher (RR = 3.3; 95% CI: 2.5, 4.4).

Diagnostic performance varied by pathology grade. Sensitivity for progression in non-dysplastic BE was 42%, while specificity was 96%. For low-grade dysplasia or indefinite for dysplasia, sensitivity was 77% and specificity was 76%. The authors note that these diagnostic characteristics are currently suboptimal, which precludes uniform clinical adoption. Prospective studies with standardized grading protocols are needed to determine if p53-guided surveillance improves patient outcomes.

How this fits prior evidence

This meta-analysis addresses a gap in identifying biomarkers for progression in Barrett's esophagus. It complements the finding that the TSP-9 test predicts progression to HGD/EAC as an associative risk marker. While both p53 and TSP-9 serve as risk markers, the authors of this meta-analysis note that p53 diagnostic characteristics are currently suboptimal for uniform clinical adoption.

Researchers analyzed 27 different studies to look at how p53 immunohistochemistry relates to the progression of Barrett's esophagus. The study focused on identifying patients who might be at a higher risk of developing advanced conditions, such as high-grade dysplasia or esophageal adenocarcinoma.

The findings showed that patients with abnormal p53 expression had a much higher rate of progression compared to those without it. Specifically, the rate was 8 per 100 person-years for those with the marker, versus only 0.3 per 100 person-years for those without it. Some studies even showed a risk ratio of over 10 for progression in certain groups.

While the test shows high specificity for certain cases, the overall diagnostic performance is currently considered inconsistent. Because the results are not yet uniform, doctors cannot use this test as a standard tool just yet. More large-scale studies are needed to see if using p53 to guide check-ups actually improves patient outcomes.

What this means for you:

Abnormal p53 expression is linked to higher cancer risk in Barrett's esophagus, but more research is needed.

Common questions

What is the risk of progression for patients with abnormal p53?

The study found that the rate of progression for patients with abnormal p53 expression was 8 per 100 person-years. In comparison, the rate for patients without abnormal p53 was much lower, at 0.3 per 100 person-years.

How accurate is the p53 test for identifying risk?

The test has a specificity of 96% for non-dysplastic Barrett's esophagus and 76% for low-grade dysplasia. However, the study notes that the diagnostic characteristics are currently not consistent enough for wide use in clinical practice.

Can doctors use p53 tests to decide on treatment plans now?

Not yet. While the link between p53 and progression is clear, the study states that more research is needed to see if p53-guided strategies actually improve patient outcomes. You should talk to your doctor about your specific results.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedOct 2026

PMID41738629

View Original Abstract ↓

INTRODUCTION: The adjunctive use of p53 immunohistochemistry has been proposed as a potential tool to improve risk stratification in Barrett's esophagus (BE) with conflicting results. We performed a systematic review and meta-analysis to evaluate the performance of p53 in predicting progression to advanced neoplasia (high-grade dysplasia [HGD] and esophageal adenocarcinoma [EAC]) among patients with BE. METHODS: We searched multiple databases for studies that evaluated the use of aberrant p53 in esophageal biopsies among patients with BE and reported progression rates to HGD/EAC. The outcomes were p53 test characteristics and incidence and risk ratio (RR) for progression to HGD/EAC in patients with and without aberrant p53 using random effects models. RESULTS: Among the 27 included studies, the proportion of patients with aberrant p53 expression at baseline was 20% (95% CI: 14%, 27%). The rate of progression with and without aberrant p53 was 8 per 100 person-years (95% CI: 6, 11) and 0.3 per 100 person-years (95% CI: 0.1, 0.6), respectively. Compared with patients without aberrant p53 expression, those with aberrant p53 had a higher risk for progression to HGD/EAC in cohort studies (RR = 10.2 [95% CI: 6.9, 15.0]) and case control studies (RR = 3.3 [95% CI: 2.5, 4.4]). The sensitivity for progression for non-dysplastic Barrett's esophagus and low-grade dysplasia/indefinite for dysplasia was 42% and 77% and specificity was 96% and 76%, respectively. DISCUSSION: While aberrant p53 expression has been associated with an increased risk of progression to advanced neoplasia in patients with BE undergoing surveillance, the diagnostic characteristics are suboptimal precluding uniform clinical adoption. Prospective studies with standardized grading protocols are needed to determine whether p53-guided surveillance strategies can meaningfully improve patient outcomes.

Aberrant p53 expression is associated with higher risk of progression to advanced neoplasia in Barrett's esophagusp53 Expression Linked to Higher Risk of Barrett's Esophagus Progression

How this fits prior evidence

Common questions

Study Details

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Aberrant p53 expression is associated with higher risk of progression to advanced neoplasia in Barrett's esophagusp53 Expression Linked to Higher Risk of Barrett's Esophagus Progression

How this fits prior evidence

Common questions

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