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Updated: Sep 20, 2025
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
PRAME immunohistochemistry for melanoma diagnosis: A STARD-compliant diagnostic accuracy study
Michaela K O'Connor1, Hongyan Dai1, Garth R Fraga1
1Department of Pathology and Laboratory Medicine, University of Kansas School of Medicine, Kansas City, Kansas, USA.
Background:
Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated antigen that is frequently expressed in cutaneous melanoma and can be evaluated by immunohistochemistry. Earlier studies on PRAME utilized case-control study designs that may misestimate diagnostic accuracy and lack generalizability.
Methods:
Using retrospective cohort selection, a cross-sectional study of diagnostic accuracy of PRAME was conducted according to standards for reporting diagnostic accuracy studies 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 the posttest probability of melanoma. PRAME ≤25% (0/1+) favors nevus, PRAME 26%-75% (2/3+) is noncontributory, and PRAME >75% (4+) favors melanoma.
Insights
Preferentially expressed antigen in melanoma (PRAME) is an effective diagnostic test for melanoma. Higher PRAME expression levels correlate with increased melanoma likelihood, aiding clinical diagnosis.
Area of Science:
- Dermatopathology
- Oncology
- Diagnostic Accuracy Studies
Background:
- Preferentially expressed antigen in melanoma (PRAME) is a tumor antigen frequently found in cutaneous melanoma.
- Immunohistochemistry can evaluate PRAME expression.
- Previous case-control studies may have limited generalizability and misestimated diagnostic accuracy.
Purpose of the Study:
- To evaluate the diagnostic accuracy of PRAME expression in distinguishing melanoma from benign melanocytic lesions.
- To assess PRAME as a diagnostic marker using a retrospective cohort design.
Main Methods:
- A cross-sectional study design adhering to Standards for Reporting Diagnostic Accuracy studies (STARD) requirements.
- Retrospective cohort selection of melanocytic lesions.
- Immunohistochemical evaluation of PRAME expression.
Main Results:
- PRAME expression was significantly higher in malignant melanocytic lesions (n=42) compared to benign lesions (n=101) (0.71 ± 0.30 vs. 0.13 ± 0.20, p < 0.01).
- Receiver operating characteristic curve analysis indicated effective test performance (Area Under Curve = 0.90).
- PRAME 4+ scores (>75%) demonstrated 63% sensitivity, 97% specificity, and 87% accuracy with excellent interrater concordance (Kappa = 0.83).
Conclusions:
- PRAME is an effective diagnostic test for melanoma in clinical practice.
- PRAME is best utilized as an ordinal variable to calculate posttest melanoma probability.
- Specific PRAME expression thresholds (≤25% favors nevus, 26-75% is noncontributory, >75% favors melanoma) aid in diagnosis.
