TP53 and esophageal squamous cell carcinoma: Since mutations in TP53 are found in virtually all ESCC [37, 38] and occur frequently in BE and EAC [39], it is plausible to assume that the first mutation in the field-defect involves TP53 LOH, associated with loss of TP53 tumor suppressor function, followed by a malignant transformation in response (or due) to the loss of TP53 control consistent with Knudson’s two-hit model [40].