Diffuse PRAME Expression Is Highly Specific for Thin Melanomas in the Distinction from Severely Dysplastic Nevi but Does Not Distinguish Metastasizing from Non-Metastasizing Thin Melanomas
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Updated: Oct 25, 2025
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Maximilian Gassenmaier1, Matthias Hahn1, Gisela Metzler1
1Department of Dermatology, Eberhard Karls University of Tübingen, 72076 Tübingen, Germany.
Background:
PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry is increasingly used as diagnostic adjunct in the evaluation of melanocytic tumors. The expression and prognostic significance of PRAME in melanomas ≤1.0 mm and its diagnostic utility in the distinction from severely dysplastic compound nevi (SDN) have not been studied.
Methods:
We investigated and compared the immunohistochemical PRAME expression in 70 matched thin metastasizing and non-metastasizing melanomas and 45 nevi from patients with long-term follow-up (35 SDN and 10 unequivocally benign compound nevi).
Results:
Diffuse PRAME staining in >75% of lesional epidermal and dermal melanocytes identified 58.6% of thin melanomas but did not distinguish metastasizing from non-metastasizing melanomas (p = 0.81). A superficial atypical melanocytic proliferation of uncertain significance, in which the final diagnostic interpretation favored a SDN was the only nevus with diffuse PRAME expression (1/45). Melanomas and SDN with PRAME immunoreactivity exhibited different staining patterns. Most melanomas (67.6%) showed uniform PRAME expression in the in situ and invasive component, whereas most SDN (81.0%) showed a decreasing gradient with depth.
Conclusion:
Diffuse intraepidermal and dermal PRAME staining is highly specific for melanomas in the distinction from SDN. PRAME expression is not a prognostic biomarker in melanomas ≤1.0 mm.
Insights
Preferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry is specific for distinguishing melanomas from severely dysplastic nevi. PRAME expression does not predict prognosis in thin melanomas.
Area of Science:
- Dermatopathology
- Oncology
- Immunohistochemistry
Background:
- Preferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry is a valuable tool for diagnosing melanocytic tumors.
- The role of PRAME in thin melanomas (≤1.0 mm) and its ability to differentiate from severely dysplastic nevi (SDN) remain unclear.
Purpose of the Study:
- To evaluate PRAME expression in thin melanomas and compare it with SDN.
- To determine if PRAME expression has prognostic significance in thin melanomas.
Main Methods:
- Immunohistochemical PRAME expression was analyzed in 70 thin melanomas and 45 nevi (35 SDN, 10 benign nevi).
- Metastasizing and non-metastasizing melanomas were compared.
- Staining patterns in melanomas and SDN were characterized.
Main Results:
- Diffuse PRAME staining identified 58.6% of thin melanomas but did not differentiate between metastasizing and non-metastasizing tumors.
- Only one nevus (SDN) showed diffuse PRAME expression.
- Melanomas typically exhibited uniform PRAME staining, while SDN showed a decreasing gradient.
Conclusions:
- Diffuse PRAME staining is highly specific for identifying melanomas and distinguishing them from SDN.
- PRAME is not a prognostic biomarker for melanomas ≤1.0 mm.
