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

Maximilian Gassenmaier; Matthias Hahn; Gisela Metzler; Jürgen Bauer; Amir Sadegh Yazdi; Ulrike Keim; Claus Garbe; Nikolaus Benjamin Wagner; Stephan Forchhammer

doi:10.3390/cancers13153864

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

Cancers (Basel). 2021 Jul 31;13(15):3864. doi: 10.3390/cancers13153864.

Authors

Maximilian Gassenmaier¹, Matthias Hahn¹, Gisela Metzler¹, Jürgen Bauer², Amir Sadegh Yazdi³, Ulrike Keim¹, Claus Garbe^{1

2}, Nikolaus Benjamin Wagner⁴, Stephan Forchhammer¹

Affiliations

¹ Department of Dermatology, Eberhard Karls University of Tübingen, 72076 Tübingen, Germany.
² Dermatologie in Stuttgart, 70173 Stuttgart, Germany.
³ Department of Dermatology and Allergology, University Hospital RWTH Aachen, 52074 Aachen, Germany.
⁴ Department of Dermatology, Venereology and Allergology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland.

Abstract

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.

Keywords: PRAME; dysplastic nevus; histopathology; immunohistochemistry; melanoma; metastasis; nevus; prognosis.