Abstract

Background: Preferentially expressed Antigen in Melanoma (PRAME) is a tumor-associated antigen which is frequently expressed in cutaneous melanoma and can be evaluated by immunohistochemistry. Earlier studies on PRAME utilized case-control study designs which may misestimate diagnostic accuracy and lack generalizability. Hypothesis: We hypothesized the PRAME positive likelihood ratio [sensitivity/(1- specificity)] was greater than 10. Methods: Using retrospective cohort selection, a cross-sectional study of diagnostic accuracy of PRAME was conducted according to Standards for Reporting Diagnostic accuracy studies (STARD) requirements. Results: Mean PRAME positive fraction was higher in 42 malignant melanocytic lesions than 101 benign melanocytic lesions (0.71 + 0.30 vs. 0.13 + 0.20, P < 0.01). Receiver operating characteristic curve showed the test was effective (area under the curve = 0.90). Global PRAME 4+ scores (>75%) were associated with sensitivity of 0.63, specificity of 0.97, accuracy of 0.87, and excellent interrater concordance (Kappa= 0.83). Lower cutoffs for PRAME of 2+ (>25%) and 3+ (>50%) produced higher joint sensitivity/specificity (Youden index) than PRAME 4+, but lower accuracy. Conclusion: PRAME as it is used in clinical practice is an effective test for melanoma. PRAME is best used as an ordinal variable to calculate post-test probability of melanoma. PRAME < 25% (0/1+) favors nevus, PRAME 26-75% (2/3+) is noncontributory, and PRAME > 75% (4+) favors melanoma.

Financial Disclosure:
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