Based on immuno-reactive score (IRS) analysis, we noted that NRF2 was localized predominantly in cell nuclei, and both nuclear and cytosolic NRF2 levels increased significantly with malignant progression, i.e., progression from tumor-adjacent normal epithelia to epithelial dysplasia to squamous cell carcinoma (Figure 1B). This evidence concerns the gene NFE2L2 and intraepithelial neoplasia.