Compartment-Specific Changes in SESN2 and NRF2 Expression Following Narrowband UVB Therapy in Early-Stage Mycosis Fungoides

Background and Objectives: Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma, and oxidative stress within the tumor microenvironment may contribute to its pathogenesis and treatment response. Sestrin 2 (SESN2) and nuclear factor erythroid 2-related factor 2 (NRF2) are key regulators of cellular responses to oxidative stress. This study aimed to evaluate changes in epidermal and dermal SESN2 and NRF2 expression following narrowband ultraviolet B (NB-UVB) therapy in patients with early-stage MF. Materials and Methods: This retrospective observational study included 29 patients with stage IA–IIA MF treated with NB-UVB phototherapy. Paired skin biopsies obtained from the same anatomical site before treatment and after histopathological remission were evaluated immunohistochemically for epidermal and dermal SESN2 and NRF2 expression. Staining intensity, positivity, and H-scores were assessed semiquantitatively. Results: Following NB-UVB therapy, dermal NRF2 staining intensity, positivity, and H-score decreased significantly (all unadjusted p ≤ 0.002), and these differences remained significant after adjustment for multiple comparisons. Epidermal SESN2 positivity and H-score increased in the unadjusted analyses (p = 0.047 and p = 0.030, respectively), but these differences did not remain statistically significant after adjustment. No significant changes were observed in dermal SESN2 or epidermal NRF2 expression. Changes in SESN2 and NRF2 H-scores were not significantly associated with cumulative NB-UVB dose. No significant associations were identified between SESN2 or NRF2 expression parameters and time to histopathological remission. Conclusions: Histopathological remission following NB-UVB therapy in early-stage MF was associated with significantly reduced dermal NRF2 expression after adjustment for multiple comparisons, whereas no statistically significant changes were observed in epidermal NRF2 or epidermal and dermal SESN2 expression. Further studies are required to determine whether the reduction in dermal NRF2 reflects changes in the cellular composition of the infiltrate, altered expression within individual cells, or both.