Endothelial protein C receptor expression as a marker of reduced metastatic risk in primary melanoma

Malignant melanoma has a strong propensity for early metastatic dissemination, yet conventional clinicopathological predictors such as Breslow thickness do not fully capture individual metastatic risk. The endothelial protein C receptor (EPCR) exerts context-dependent functions across malignancies, but its clinical significance in melanoma remains unclear. We retrospectively analyzed primary tumor specimens from 62 patients with invasive melanoma; 61 with complete outcome data formed the analytic cohort for metastasis analyses. EPCR expression in melanoma cells was evaluated by immunohistochemistry using semi-quantitative intensity and extent scores (0-3). Tumor-infiltrating lymphocytes were graded according to the Melanoma Institute Australia scoring system. Higher EPCR expression was associated with lower odds of documented lymph-node and distant metastatic involvement. In prespecified parsimonious multivariable logistic regression models adjusted for tumor thickness and ulceration, higher EPCR extent remained independently associated with reduced lymph-node involvement (adjusted odds ratio: 0.36, 95% confidence interval:, 0.17-0.70). EPCR expression showed a positive association with CD8+ tumor-infiltrating lymphocyte scores. Higher EPCR expression in primary melanoma was independently associated with reduced lymph-node involvement and with a CD8+-inflamed tumor microenvironment, suggesting EPCR may complement conventional pathological predictors of metastatic risk.