One Pathway for Esophageal Cancer?

Molecular profiling reveals precursor signals in BE-negative esophageal cancer

May 7, 2026
2 min

The Pathologist

Objective:

To investigate whether esophageal adenocarcinoma (EAC) can develop independently of Barrett’s esophagus (BE) and to clarify the biological pathways involved.

Key Findings:

Approximately half of EAC patients do not have detectable BE at diagnosis.
Patients with and without detectable BE share similar demographic and risk factor profiles.
Key driver mutations (CDKN2A, TP53, ARID1A) are present in both BE-positive and BE-negative tumors.
Genomic features and mutational signatures are comparable across both groups.
Markers of intestinal metaplasia were found in tumors without histologically identifiable BE.

Interpretation:

EAC may develop through a common pathway involving intestinal metaplasia, suggesting that the absence of detectable BE does not rule out underlying precursor changes.

Limitations:

The study is limited to a specific population in the UK, which may affect generalizability.
Further research is needed to explore the clinical implications of these findings.