Current Clinical Utility of Gene Expression Panels in Primary Cutaneous Melanoma

Roughly 100,000 new cases of melanoma are diagnosed yearly in the United States, the majority of which are early-stage disease with excellent prognosis. However, a subset of patients harbors clinically occult aggressive biology that can go undetected on standard clinicopathologic analyses. Gene expression profiling (GEP) assays have emerged as molecular adjuncts to risk stratification, aiming to improve sentinel lymph node biopsy (SLNB) decision-making and surveillance planning. Two commercial tests are widely available: the 31-gene expression profile (31-GEP, DecisionDx-Melanoma, Castle Biosciences) and the clinicopathologic gene expression profile (CP-GEP, Merlin, SkylineDx). This review summarizes the current evidence for each assay regarding their performance and utility, with a focus on potentially actionable use cases, limitations, and the practical context in which these tools are most valuable.