PRAME

PRAME is an acronym for “Preferentially Expressed Antigen in Melanoma.” PRAME is a melanoma-associated antigen that was isolated from a melanoma patient’s autologous T cells. PRAME is a cancer-testis antigen ( see “Notes”) that may be overexpressed in many malignant tumors, including ocular melanoma. The tumor cells produce increased levels of PRAME mRNA and PRAME protein. PRAME is detected through gene expression analysis, quantitative PCR, or immunohistochemistry.

PRAME and Uveal Melanoma: Increased expression of the PRAME gene is an independent marker of poor prognosis in Uveal Melanoma. In this type of melanoma, molecular PRAME activity serves to further stratify the risk of tumors in the prognostically more favorable gene expression class 1; PRAME-positive class 1 tumors exhibit a significantly higher risk of metastasis than PRAME-negative tumors. Elevated expression may indicate a biologically more aggressive tumor cell population (Field et al. Clinical Cancer Research 2016).

PRAME and cutaneous melanomas: Among the cutaneous melanoma subtypes, PRAME was diffusely expressed in 94.4% of acral melanomas, 92.5% of superficial spreading melanomas, 90% of nodular melanomas, in 88.6% of lentigo maligna melanomas, and in 35% of desmoplastic melanomas. Between 86.4% and 96.1% of common melanocytic nevi were found to be completely PRAME-negative. Immunoreactivity for PRAME in small melanocyte subpopulations can be observed in approximately 13.6% of cutaneous nevi, including dysplastic nevi (in a larger study, approximately 13% of dysplastic nevi were found to be diffusely PRAME-positive/Turner N et al. 2024). PRAME reactivity can also be found in traumatized nevi or Spitz nevi, although no clinical conclusions can be drawn from this (Lezcano C et al. 2018). In various studies, PRAME demonstrated a sensitivity of 89.6% and a specificity of 96.1% in distinguishing between melanomas and nevi (Bahmad HF et al. 2023). Among non-melanocytic lesions, some poorly differentiated tumors, including atypical fibroxanthomas, may be PRAME-positive (Turner N et al. 2024; Lezcano C et al. 2018; Bahmad HF et al. 2023)

Cancer-testis antigens (CTAs) are proteins whose expression is normally largely restricted to germ cells in the testis—and to some extent also in the placenta and ovary—but which are abnormally reactivated in numerous malignant tumors. The name therefore means:

• Cancer: Expression in various tumor cells
• Testis: Physiological expression primarily in male germ cells
• Antigen: The protein can be recognized by the immune system

In most normal somatic tissues, the corresponding genes are epigenetically silenced. In tumor cells, DNA hypomethylation in particular can lead to their reactivation. Since testicular germ cells express very few HLA class I molecules and are immunologically shielded, a pronounced immune tolerance to these antigens often does not develop. As a result, CTAs can trigger a tumor-specific immune response. Well-known examples include MAGE-A1/A3/A4, NY-ESO-1, SSX, CTAG2, and PRAME.

1. Bahmad HF et al. (2023) Potential diagnostic utility of PRAME and p16 immunohistochemistry in melanocytic nevi and malignant melanoma. J Cutan Pathol 50:763-772.
2. Field MG et al. (2016) PRAME as an Independent Biomarker for Metastasis in Uveal Melanoma. Clin Cancer Res 22:1234–1242.
3. Lezcano C et al. (2018) PRAME Expression in Melanocytic Tumors. Am J Surg Pathol 42: 1456–1465.
4. Salzano S et al. (2025) Preferentially Expressed Antigen in Melanoma (PRAME) as a Diagnostic and Predictive Marker in Melanocytic Tumors: An Updated Narrative Review. Histol Histopathol 40:1889–1895
5. Turner N et al. (2024) Pitfalls of PRAME Immunohistochemistry in a Large Series of Melanocytic and Nonmelanocytic Lesions With Literature Review. Am J Dermatopathol 46:21-30.