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Published on: March 8, 2022
PRAME Immunostaining in Acral Melanocytic Proliferations: A Meta-Analysis
Ana L Toussaint1, Carlos Sánchez-Cárdenas2, Ruth Fuentes-García1
1School of Sciences, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Abstract:
Acral cutaneous melanoma is a highly aggressive form of skin cancer that develops in palms, soles, and/or the nail unit. PReferentially expressed Antigen in MElanoma (PRAME) is an immunohistochemical marker that has shown a high degree of expression in cutaneous melanomas. However, no meta-analysis has previously focused on acral melanocytic proliferations. Herein, we performed the first meta-analysis to objectify the utility of PRAME immunohistochemistry, focusing on this understudied subtype of melanocytic proliferations involving acral sites. Thirteen studies were identified, which included 930 lesions (557 malignant and 373 benign). A random-effects model was used to calculate sensitivity, specificity, and likelihood ratios. Summary receiver operating characteristic curves and forest plots were created, and heterogeneity was assessed using Cochran Q and I2 statistics. PRAME expression in acral melanoma showed the highest diagnostic accuracy at a cutoff value of 3+/50%, pertaining to the optimal balance between sensitivity and specificity (78% and 92%, respectively). Although PRAME immunostaining enhances the accurate diagnosis of acral melanocytic proliferations, its expression in atypical and borderline melanocytic proliferations remains controversial and shows considerable variability. Thus, the definitive diagnosis of acral melanoma still relies on careful clinicopathologic assessment and, occasionally, molecular correlation.
Insights
PRAME immunohistochemistry aids in diagnosing acral melanoma, a rare skin cancer. This meta-analysis found PRAME expression has high accuracy, but definitive diagnosis still requires clinicopathologic assessment.
Area of Science:
- Dermatology
- Oncology
- Pathology
Background:
- Acral cutaneous melanoma is an aggressive skin cancer on palms, soles, and nail units.
- PReferentially expressed Antigen in MElanoma (PRAME) is a marker highly expressed in melanomas.
- No prior meta-analysis focused on PRAME utility in acral melanocytic proliferations.
Purpose of the Study:
- To conduct the first meta-analysis on PRAME immunohistochemistry for diagnosing acral melanocytic proliferations.
- To objectively evaluate the diagnostic utility of PRAME in this specific subtype of melanoma.
Main Methods:
- Systematic review and meta-analysis of 13 studies involving 930 acral lesions (557 malignant, 373 benign).
- Utilized random-effects models to calculate diagnostic accuracy metrics (sensitivity, specificity, likelihood ratios).
- Assessed heterogeneity using Cochran Q and I2 statistics; generated summary receiver operating characteristic curves.
Main Results:
- PRAME expression demonstrated high diagnostic accuracy for acral melanoma at a cutoff of 3+/50%, with 78% sensitivity and 92% specificity.
- PRAME immunostaining improves diagnosis of acral melanocytic proliferations.
- Expression in atypical and borderline lesions showed variability and remains controversial.
Conclusions:
- PRAME immunohistochemistry is a valuable tool for enhancing the diagnosis of acral melanoma.
- Definitive diagnosis of acral melanoma necessitates comprehensive clinicopathologic evaluation, potentially including molecular correlation.
- Further research is needed to clarify PRAME's role in borderline and atypical acral melanocytic lesions.
