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PRAME immunohistochemistry

PRAME; preferentially expressed antigen in melanoma

PRAME (preferentially expressed antigen in melanoma) immunohistochemistry has become an important adjunct in the workup of ambiguous melanocytic lesions. Diffuse nuclear PRAME positivity (≥ 75% of melanocytes) supports melanoma over benign naevus; patchy or absent staining argues against melanoma. PRAME does not replace conventional histology and is not infallible — Spitz, blue, deep penetrating and pigmented epithelioid melanocytomas can be patchy or positive — but it adds diagnostic discriminatory power, particularly in difficult lentigo maligna / pigmented actinic keratosis cases, ambiguous spitzoid lesions and questions of margin involvement.

CurrentLast reviewed 15 May 2026

Background

  • PRAME is a cancer-testis antigen physiologically expressed only in germ-line tissue (testis, oocyte) and re-activated in many cancers including melanoma.
  • Detected by IHC on FFPE tissue; commercial monoclonal antibody clone EPR20330 widely used.
  • Scoring — percentage of nuclear-stained melanocytes: 0 (negative), 1+ (1–25%), 2+ (26–50%), 3+ (51–75%), 4+ (> 75%, diffuse).
  • Diffuse positivity (3+/4+) strongly supports melanoma.

When to request PRAME

  • Ambiguous melanocytic lesion where the question is benign naevus vs melanoma.
  • Lentigo maligna vs pigmented actinic keratosis vs solar lentigo — particularly where conventional histology is borderline.
  • Atypical spitzoid lesion (atypical Spitz tumour vs spitzoid melanoma).
  • Confirming melanoma at a difficult margin (e.g. confluent atypical junctional component vs background sun damage).
  • Distinguishing melanoma in situ from severely dysplastic naevus.

Limitations and pitfalls

  • Spitz naevi — some show 2+/3+ patchy staining; not diagnostic of melanoma in isolation.
  • Deep penetrating naevi, pigmented epithelioid melanocytomas — can be 2+/3+; correlate with other features.
  • Blue naevi — variable.
  • Some melanomas — particularly desmoplastic — are PRAME negative.
  • PRAME is one piece of evidence; integrate with conventional histology, dermoscopy and clinical context.
  • Quality control — laboratory validation of antibody and protocol is essential; results from non-validated labs unreliable.

Integration with conventional pathology

  • PRAME complements but does not replace H&E and traditional melanocytic markers (S100, SOX10, Melan-A, HMB-45).
  • MyPath Melanoma, mRNA-based GEP tests are alternative ancillary tools — debated evidence base, see editorial-policy.
  • Comparative genomic hybridisation (CGH) and next-generation sequencing for melanoma-defining genomic events (chromosomal copy number changes, TERT promoter mutations) remain the reference standard for ambiguous lesions in difficult cases.
  • MDT discussion of every ambiguous melanocytic case is essential — pathology alone is rarely definitive.

References

  1. Lezcano C et al. PRAME expression in melanocytic tumors by immunohistochemistry. Am J Surg Pathol; 2018.
  2. Gradecki SE et al. PRAME immunohistochemistry as an adjunct to melanocytic pathology. J Cutan Pathol; 2020.

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