Genetic Variation in Background Mucosa Across Different Grades of Chronic Esophagitis

The risk of cancer in chronic esophagitis varies by the number of Lugol's voiding lesions (LVLs). However, how these mutations differ by LVLs grade remains unclear. We aimed to clarify the genetic characteristics of the background mucosa by LVLs grade with a history of endoscopic treatment for esophageal squamous cell carcinoma (ESCC) or squamous dysplasia (SD).

A total of 34 patients (28 ESCC, 6 SD) were classified by LVLs grade. Tissues from ESCC/SD and background mucosa were taken endoscopically, and DNA was extracted. Somatic mutations were identified in the esophageal cancer panel. For each mutation, putative drivers were identified by OncoKB, and the gene mutation patterns were compared among the grades.

There were LVLs grade B/C = 14/20 cases. Somatic mutation of TP53 was found significantly more frequently in the LVLs than in the background mucosa (88.2% vs. 64.7%, p = 0.043, Fisher's exact test). Somatic mutations of NOTCH1, including putative drivers, were more frequent in the background mucosa than in ESCC/SD (82.3% vs. 44.1%, p = 0.002, Fisher's exact test). There was no significant difference in the percentage of putative drivers of TP53 and NOTCH1 in the background mucosa by LVLs grade B/C (50.0% vs. 35.0%, p = 0.487; 7.1% vs. 5.0%, p = 1.000, Fisher's exact test).

Regardless of LVLs grade, the background mucosa of patients with chronic esophagitis who already had ESCC or SD had already accumulated the same level of TP53 gene mutations. Even patients with LVLs grade B chronic esophagitis should undergo regular endoscopic examination for early detection of ESCC.