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Updated: Nov 5, 2025

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Preferentially Expressed Antigen in Melanoma Immunostaining in a Series of Melanocytic Neoplasms
Paul B Googe1,2, Kendall L Flanigan3, Jayson R Miedema1,2
1Departments of Dermatology, and.
Abstract:
In their 2018 article, Lezcano et al [AJSP 2018(11):1456] show that diffuse tumor cell nuclear reactivity for Preferentially expressed Antigen in Melanoma (PRAME) is a feature of melanoma and that benign and atypical melanocytic tumors are PRAME negative or show only focal positivity for PRAME. We report our observations of PRAME staining in 253 melanocytic tumors. Tumors were classified by hematoxylin and eosin sections. The nuclear PRAME staining of neoplastic melanocytes in each case was categorized as absent, focally present, or diffusely present. The results were compared with those of Lezcano et al 105 of 134 (78%) melanocytic nevi were completely PRAME negative. Of the 29 PRAME-positive benign lesions, 28 exhibited focal but not diffuse positivity, including atypical (n = 11) and dysplastic nevi (n = 11). One of 11 Spitz nevi showed diffuse positivity (9%). Thirty-nine of 51 (76%) invasive melanomas, 41 of 50 (82%) melanoma in situ, and 15 of 18 (83%) metastatic melanomas were diffusely PRAME positive. Excluding desmoplastic melanomas, 39 of 49 (80%) primary melanomas were diffusely PRAME positive. Our findings of PRAME staining in melanocytic neoplasia are in general agreement with those of Lezcano et al. Diffuse PRAME reactivity in neoplastic melanocytes is a feature of malignancy and was only otherwise seen in 1 Spitz nevus. Caution is advised in interpretation of PRAME reactivity in melanocytic tumors of uncertain classification because melanoma arising in association with nevus and some atypical melanocytic tumors may show focal or incomplete PRAME staining. Routine histopathological findings, clinical information, PRAME staining, and judicious application of molecular studies are steps leading to accurate classification of melanocytic neoplasia.
Insights
Diffuse nuclear reactivity for Preferentially expressed Antigen in Melanoma (PRAME) reliably indicates melanoma malignancy. While most benign and atypical melanocytic tumors are PRAME-negative, focal staining can occur, necessitating careful interpretation alongside other diagnostic methods.
Area of Science:
- Dermatopathology
- Oncology
- Molecular Diagnostics
Background:
- Preferentially expressed Antigen in Melanoma (PRAME) staining differentiates melanoma from benign nevi.
- Previous studies indicate PRAME is negative or focally positive in benign/atypical melanocytic tumors.
Purpose of the Study:
- To evaluate PRAME staining patterns in a large cohort of melanocytic tumors.
- To compare findings with existing literature and assess PRAME's diagnostic utility.
Main Methods:
- Retrospective analysis of 253 melanocytic tumors.
- Classification based on hematoxylin and eosin (H&E) staining.
- Categorization of nuclear PRAME reactivity as absent, focal, or diffuse.
Main Results:
- 78% of melanocytic nevi were PRAME-negative.
- Focal PRAME positivity was observed in 28/29 benign lesions, including atypical and dysplastic nevi.
- Diffuse PRAME positivity was found in 76-83% of invasive, in situ, and metastatic melanomas.
Conclusions:
- Diffuse PRAME reactivity is a strong indicator of melanoma malignancy.
- Focal PRAME staining in some atypical nevi and Spitz nevi requires cautious interpretation.
- Integrating PRAME staining with histopathology, clinical data, and molecular studies aids accurate melanocytic neoplasia classification.

