# Diagnostic Utility of PRAME Expression in Melanocytic Lesions: Cut-Off Threshold Analysis

## TL;DR

This study evaluates PRAME as a marker for diagnosing melanoma, finding that a 50% threshold best balances accuracy in distinguishing melanoma from benign lesions.

## Contribution

The study introduces a validated 50% PRAME expression threshold for improved melanoma diagnosis accuracy.

## Key findings

- PRAME expression at 50% threshold showed 92.3% sensitivity and 96.8% specificity for melanoma diagnosis.
- A 50% threshold better differentiates melanoma from dysplastic, compound, and blue nevi compared to 75%.
- PRAME was occasionally positive in benign nevi and negative in one melanoma case.

## Abstract

Background/Objectives: PRAME (Preferentially Expressed Antigen in Melanoma) is a promising immunohistochemical marker for distinguishing melanoma from benign melanocytic lesions, though optimal thresholds remain uncertain. This study evaluated PRAME expression in melanocytic lesions and compared diagnostic accuracy using two thresholds. Methods: We retrospectively assessed PRAME expression in 145 melanocytic lesions diagnosed between 2016 and 2021 at Istanbul Training and Research Hospital: 52 melanomas, 27 dysplastic nevi, 23 Spitz nevi, 15 compound nevi, 23 blue nevi, and 5 congenital nevi. Immunohistochemical staining (PRAME EP461, Cell Marque) was scored semi-quantitatively based on nuclear positivity: 0 (negative), 1 (1–24%), 2 (25–49%), 3 (50–74%), and 4 (≥75%). Diagnostic accuracy was evaluated at 50% and 75% thresholds. Results: PRAME expression at both thresholds was significantly higher in melanomas than nevi (p < 0.05). Sensitivity and specificity were 92.3% and 96.8% at 50%, and 82.7% and 98.9% at 75%. Lowering the threshold to 50% improved sensitivity with minimal specificity loss, particularly differentiating melanoma from dysplastic, compound, and blue nevi. Occasional positivity was observed in Spitz and dysplastic nevi; one melanoma was PRAME-negative. Conclusions: PRAME is an effective marker for melanoma diagnosis. A 50% threshold optimizes sensitivity while preserving specificity; however, histopathological evaluation remains the gold standard, and PRAME should be used only as an adjunct to avoid potential overdiagnosis, particularly in borderline lesions.