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Diagnostic Utility of PRAME Expression in Melanocytic Lesions: Cut-Off Threshold Analysis
Beste Noyan Mod1, Cem Leblebici2
1Department of Pathology, Basaksehir Cam and Sakura City Hospital, University of Health Sciences, 34480 Istanbul, Turkey.
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.
Insights
PRAME (Preferentially Expressed Antigen in Melanoma) is a valuable marker for melanoma diagnosis. A 50% expression threshold offers the best balance of sensitivity and specificity, aiding in distinguishing melanoma from benign lesions.
Area of Science:
- Dermatopathology
- Oncology
- Immunohistochemistry
Background:
- PRAME is a promising immunohistochemical marker for melanoma detection.
- Optimal PRAME expression thresholds for diagnostic accuracy are uncertain.
- Distinguishing melanoma from benign melanocytic lesions is clinically significant.
Purpose of the Study:
- To evaluate PRAME expression in various melanocytic lesions.
- To compare diagnostic accuracy of PRAME using 50% and 75% thresholds.
- To determine the optimal threshold for PRAME in melanoma diagnosis.
Main Methods:
- Retrospective analysis of 145 melanocytic lesions (52 melanomas, 93 benign nevi).
- Immunohistochemical staining for PRAME (EP461) with semi-quantitative scoring.
- Diagnostic accuracy assessed using 50% and 75% nuclear positivity thresholds.
Main Results:
- PRAME expression was significantly higher in melanomas versus nevi (p < 0.05).
- At 50% threshold: sensitivity 92.3%, specificity 96.8%. At 75% threshold: sensitivity 82.7%, specificity 98.9%.
- The 50% threshold improved sensitivity with minimal specificity loss, aiding differentiation from specific benign nevi.
Conclusions:
- PRAME is an effective adjunct marker for melanoma diagnosis.
- A 50% threshold optimizes PRAME's diagnostic utility, balancing sensitivity and specificity.
- Histopathology remains gold standard; PRAME aids in avoiding overdiagnosis of borderline lesions.
