Prognostic Significance of STING Expression in Extramammary Paget's Disease

Background/Objectives: Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy with a highly variable clinical behavior. While early-stage disease is often indolent, progression to dermal invasion and lymph node metastasis is associated with a poor prognosis. Reliable biomarkers that reflect tumor aggressiveness and predict clinical outcomes are lacking. The stimulator of interferon genes (STING) pathway plays a central role in innate immune signaling and antitumor immunity; however, its clinical significance in EMPD remains unclear. Methods: We retrospectively analyzed STING expression using immunohistochemistry in formalin-fixed, paraffin-embedded tumor specimens obtained from 63 patients with EMPD. Associations between STING expression and clinicopathological features were evaluated. Overall survival was analyzed using Kaplan-Meier methods, and prognostic factors were assessed using univariate and multivariate Cox proportional hazards regression analyses. Results: STING expression was positive in 26 (41%) and negative in 37 (59%) patients. Loss of STING expression was significantly associated with dermal invasion and lymph node swelling. Kaplan-Meier analysis demonstrated a significantly poorer overall survival in patients with STING negativity than in those with STING positivity. In univariate analysis, lymph node swelling, dermal invasion, and STING expression were significantly associated with survival. Multivariate Cox regression analysis identified lymph node swelling as an independent adverse prognostic factor, whereas STING expression was an independent favorable prognostic factor. Loss of STING expression is closely associated with aggressive clinicopathological features and independently predicts poor prognosis in EMPD. Conclusions: STING expression may serve as a useful prognostic biomarker and provides insight into the immunobiology of EMPD.