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The Need for Standardization of PRAME Immunohistochemistry in Melanocytic Neoplasms

Calla M Sullivan1,2, Dominick DiMaio3, Scott Lauer3

  • 1Department of Dermatology, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Dermatopathology (Basel, Switzerland)
|January 21, 2026
PubMed

Insights

The PRAME immunohistochemistry stain shows poor reproducibility among dermatopathologists for diagnosing melanomas. Further research is needed for a standardized scoring method for PRAME (PReferentially expressed Antigen in MElanoma) interpretation.

Area of Science:

  • Dermatopathology
  • Oncology
  • Immunohistochemistry

Background:

  • Accurate melanoma diagnosis is critical for patient outcomes.
  • PRAME (PReferentially expressed Antigen in MElanoma) is a key immunohistochemical marker for melanoma.
  • Evaluating the reliability of PRAME scoring is essential for clinical practice.

Purpose of the Study:

  • To assess the inter-rater reliability of PRAME scoring among dermatopathologists.
  • To identify challenges in PRAME interpretation for melanocytic neoplasms.
  • To determine the need for improved PRAME scoring methodologies.

Main Methods:

  • A blinded survey of 21 melanocytic neoplasms stained with PRAME and H&E.
  • Five dermatopathologists provided PRAME scores (0-4+), percent positivity, H-score, and interpretation.
  • Statistical analysis using Kappa statistic and intraclass correlations (ICCs) for reliability assessment.

Main Results:

  • Poor inter-rater reliability was observed for PRAME score (Kappa = 0.16).
  • Low reliability was also found for percent PRAME positivity (ICC = 0.31) and H-score (ICC = 0.40).
  • Significant variation in reporting language among pathologists was noted.

Conclusions:

  • PRAME immunohistochemistry interpretation currently lacks sufficient reproducibility, particularly for difficult cases.
  • A more standardized and rigorous scoring system for PRAME is required.
  • Future studies should explore AI for PRAME interpretation to enhance reliability.
Keywords:
PRAMEimmunohistochemistrymelanomanevus

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