Absence of Lugol staining indicates initiation of esophageal squamous cell carcinoma: A combined genomic and epidemiologic study

The genomic characteristics during the carcinogenic process of esophageal squamous cell carcinoma (ESCC) remain largely unknown. We report here the genomic characteristics of 106 esophageal tissues of various stages from a population-based screening cohort in China (“Endoscopic Screening for Esophageal Cancer in China” trial) and 57 ESCC tissues from a local hospital. A significant increase in somatic mutation and copy number alterations is observed in the non-dysplastic Lugol unstaining lesions (ND-LULs). Extensive clonal expansion has emerged in the ND-LULs to an extent similar to that in higher-stage lesions. The burden of genomic alterations correlates with the size of LULs in the ND-LULs. 8-year follow-up shows that ND-LULs harbor an increased risk of progression to ESCC (adjusted IRR(6–10 mm vs. none) = 4.66, adjusted IRR(>10 mm vs. none) = 40.70), and the risk is correlated with LUL size for both non-dysplastic and dysplastic lesions. Lugol unstaining can be the initial stage in the carcinogenic process of ESCC.