Diagnostic and Prognostic Values of PRAME Immunohistochemistry in Acral Lentiginous Melanoma

BACKGROUND: PReferentially Expressed Antigen in MElanoma (PRAME) was introduced as an ancillary tool for confirming the diagnosis of cutaneous melanoma, including the acral lentiginous melanoma (ALM). However, its standardized cut-off values and prognostic performance remain inconclusive. This study assessed the diagnostic performance of PRAME immunohistochemistry (IHC) in ALM across different thresholds and explored its prognostic associations. METHODS: This retrospective cohort study reviewed 90 acral melanocytic lesions, including 60 cases of acral benign nevi and 30 cases of primary ALM. PRAME immunohistochemistry was performed on the biopsy specimens. Sensitivity and specificity were calculated at varying cut-offs. The optimal threshold was applied to link PRAME expression with the outcome and features of ALM. RESULTS: A PRAME staining threshold of 50% (score ≥3) provided the optimum cut-off for differentiating ALM, with a high specificity of 98.3% and sensitivity of 53.3%. Positive PRAME was significantly associated with higher TNM stages (ordinal odds ratio [95% confidence interval], 13.11 [2.55-67.27]) and higher rates of recurrence (hazard ratio, 6.62 [1.42-30.94]) but not with any unfavorable histopathological features or mortality. CONCLUSION: PRAME can be used as an adjunctive diagnostic tool to differentiate malignant from benign acral melanocytic lesions. It may serve as a prognostic marker for poor ALM outcomes.