Track

Clinical Studies

Abstract

Morphologically ambiguous melanocytic neoplasms may pose a diagnostic dilemma and require ancillary assays such as PRAME IHC and/or molecular testing. Studies correlating PRAME IHC with molecular assays are scarce, and no existing data suggests which cases would most benefit from molecular analysis following PRAME IHC. We compared PRAME IHC and gene expression profiling (GEP) in challenging melanocytic lesions. All cutaneous melanocytic lesions sent out for GEP (n=122) from 2014-2022 were retrieved from our institutional archives and consultation files. Statistical analysis was performed comparing PRAME IHC score (0+, 1+, 2+, 3+, or 4+, corresponding with 0%, 1-25%, 26-50%, 51-74%, and ≥75% of cells positive, respectively; and positive/negative, where a score of 4+ was considered positive) to GEP category (positive, negative, indeterminate).  PRAME score significantly correlated with GEP category (p<0.001).  PRAME and GEP were discrepant in 32 cases (26%).  GEP category varied significantly with PRAME scores of 2+, 3+, or 4+ compared with 0+, and with 4+ compared to 1+ (p < 0.001 each).  PRAME score was significantly associated with discrepancy (p<0.001) such that scores of 2+ and 3+ showed 94- and 50-fold greater rates of discrepancy, respectively, than a score of 0.  PRAME scores of 2+ or 3+ may benefit most from molecular testing as their odds of PRAME-GEP discrepancy were markedly higher. Finally, the sensitivity of GEP (0.97) for the final diagnosis was much higher (p<0.001) than PRAME (0.59), suggesting that dermatopathologists more readily consider PRAME as a false negative than GEP.