NFE2L2 and esophageal squamous cell carcinoma: One classic approach is the immunohistochemical analysis of tumor tissue specimens for the nuclear NRF2 protein [26,46,74,75,78,146] In the immunohistochemical analysis, higher NRF2 expression in ESCC than in the matched normal tissue in the same case is generally considered to signify the detection of an NRF2-addicted cancer.