PRAME Expression in Merkel Cell Carcinoma: Correlation With MCPyV Status, PD-L1, and Tumor-Infiltrating Lymphocytes in a Multicenter Cohort

Preferentially expressed antigen in melanoma (PRAME) expression has been described in Merkel cell carcinoma (MCC), but its clinicopathologic and biological significance remains incompletely characterized. We investigated PRAME expression in MCC and its relationship with Merkel cell polyomavirus (MCPyV) status, PD-L1 expression, tumor-infiltrating lymphocytes (TILs), clinicopathologic features, and clinical outcome. Thirty-five MCC cases from 3 centers were retrospectively reviewed. Histopathologic features and immunohistochemical expression of PRAME, PD-L1, MCPyV, and p53 were reassessed. PRAME positivity was defined as staining extent scores of 3+ or 4+ combined with at least moderate staining intensity. TILs were evaluated on hematoxylin and eosin sections. Clinicopathologic correlations were assessed statistically, and overall survival and distant metastasis-free survival were analyzed using Kaplan-Meier and Cox regression methods. PRAME expression was identified in 10 of 33 evaluable tumors (30.3%). Most positive cases showed diffuse nuclear staining, although one tumor demonstrated heterogeneous PRAME expression. MCPyV positivity was seen in 51.4% of cases, and PRAME expression was more frequent in MCPyV-positive tumors (P=0.057). Combined PRAME/PD-L1 positivity was associated with higher TIL density (P=0.018). PRAME expression was not associated with clinicopathologic parameters or survival. Lower PD-L1 expression (CPS <1) was independently associated with shorter overall survival. PRAME was expressed in approximately one-third of MCCs. PRAME expression was not independently associated with survival outcomes. Higher expression rates in MCPyV-positive tumors and associations with selected immune-related parameters warrant further investigation.